NM_022173.4:c.1035-7C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_022173.4(TIA1):c.1035-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000592 in 1,605,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000058 ( 0 hom. )

Consequence

TIA1
NM_022173.4 splice_region, intron

Scores

Splicing: ADA: 0.00002167

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.61

Publications

0 publications found

Variant links:

Genes affected

TIA1 (HGNC:11802): (TIA1 cytotoxic granule associated RNA binding protein) The product encoded by this gene is a member of a RNA-binding protein family and possesses nucleolytic activity against cytotoxic lymphocyte (CTL) target cells. It has been suggested that this protein may be involved in the induction of apoptosis as it preferentially recognizes poly(A) homopolymers and induces DNA fragmentation in CTL targets. The major granule-associated species is a 15-kDa protein that is thought to be derived from the carboxyl terminus of the 40-kDa product by proteolytic processing. Alternative splicing resulting in different isoforms has been found for this gene. [provided by RefSeq, May 2017]

TIA1 links:

C2orf42 (HGNC:26056): (chromosome 2 open reading frame 42) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

C2orf42 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 2-70212852-G-A is Benign according to our data. Variant chr2-70212852-G-A is described in CliVar as Likely_benign. Clinvar id is 1564800.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-70212852-G-A is described in CliVar as Likely_benign. Clinvar id is 1564800.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-70212852-G-A is described in CliVar as Likely_benign. Clinvar id is 1564800.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-70212852-G-A is described in CliVar as Likely_benign. Clinvar id is 1564800.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-70212852-G-A is described in CliVar as Likely_benign. Clinvar id is 1564800.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-70212852-G-A is described in CliVar as Likely_benign. Clinvar id is 1564800.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-70212852-G-A is described in CliVar as Likely_benign. Clinvar id is 1564800.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-70212852-G-A is described in CliVar as Likely_benign. Clinvar id is 1564800.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-70212852-G-A is described in CliVar as Likely_benign. Clinvar id is 1564800.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-70212852-G-A is described in CliVar as Likely_benign. Clinvar id is 1564800.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-70212852-G-A is described in CliVar as Likely_benign. Clinvar id is 1564800.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-70212852-G-A is described in CliVar as Likely_benign. Clinvar id is 1564800.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-70212852-G-A is described in CliVar as Likely_benign. Clinvar id is 1564800.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-70212852-G-A is described in CliVar as Likely_benign. Clinvar id is 1564800.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-70212852-G-A is described in CliVar as Likely_benign. Clinvar id is 1564800.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-70212852-G-A is described in CliVar as Likely_benign. Clinvar id is 1564800.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-70212852-G-A is described in CliVar as Likely_benign. Clinvar id is 1564800.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-70212852-G-A is described in CliVar as Likely_benign. Clinvar id is 1564800.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-70212852-G-A is described in CliVar as Likely_benign. Clinvar id is 1564800.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-70212852-G-A is described in CliVar as Likely_benign. Clinvar id is 1564800.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-70212852-G-A is described in CliVar as Likely_benign. Clinvar id is 1564800.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-70212852-G-A is described in CliVar as Likely_benign. Clinvar id is 1564800.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-70212852-G-A is described in CliVar as Likely_benign. Clinvar id is 1564800.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-70212852-G-A is described in CliVar as Likely_benign. Clinvar id is 1564800.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-70212852-G-A is described in CliVar as Likely_benign. Clinvar id is 1564800.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 10 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIA1	NM_022173.4 link	c.1035-7C>T		splice_region_variant, intron_variant	Intron 12 of 12	ENST00000433529.7	NP_071505.2	P31483-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIA1	ENST00000433529.7 link	c.1035-7C>T		splice_region_variant, intron_variant	Intron 12 of 12	2	NM_022173.4	ENSP00000401371.2		P31483-1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000279

AC:

AN:

251042

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000617

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000585

AC:

AN:

1453232

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

723544

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33284

American (AMR)

AF:

0.00

AC:

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26078

East Asian (EAS)

AF:

0.00

AC:

AN:

39624

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86052

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.0000706

AC:

AN:

1104306

Other (OTH)

AF:

0.0000666

AC:

AN:

60064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5206

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68046

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000823

Hom.:

Bravo

AF:

0.0000529

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Welander distal myopathy

Benign:1

Dec 18, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.51

PhyloP100

1.6

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000022

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over