Genetic Variant TIA1:c.223-3dupT (chr2-70229320-T-TA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_022173.4(TIA1):c.223-3dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0396 in 1,009,730 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 30)

Exomes 𝑓: 0.046 ( 0 hom. )

Consequence

TIA1
NM_022173.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -1.61

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 2-70229320-T-TA is Benign according to our data. Variant chr2-70229320-T-TA is described in ClinVar as [Benign]. Clinvar id is 1582154.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0462 (39935/864546) while in subpopulation SAS AF= 0.0503 (2411/47898). AF 95% confidence interval is 0.0487. There are 0 homozygotes in gnomad4_exome. There are 19322 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 55 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIA1	NM_022173.4 link	c.223-3dupT		splice_region_variant, intron_variant	Intron 3 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.223-3_223-2insT		splice_region_variant, intron_variant	Intron 3 of 12	2	NM_022173.4	ENSP00000401371.2		P31483-1

Frequencies

GnomAD3 genomes

AF:

0.000379

AC:

AN:

145136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000680

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000137

Gnomad ASJ

AF:

0.000296

Gnomad EAS

AF:

0.000198

Gnomad SAS

AF:

0.000218

Gnomad FIN

AF:

0.00111

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000152

Gnomad OTH

AF:

0.00151

GnomAD4 exome

AF:

0.0462

AC:

39935

AN:

864546

Hom.:

Cov.:

AF XY:

0.0451

AC XY:

19322

AN XY:

428178

show subpopulations

Gnomad4 AFR exome

AF:

0.0470

Gnomad4 AMR exome

AF:

0.0347

Gnomad4 ASJ exome

AF:

0.0494

Gnomad4 EAS exome

AF:

0.0305

Gnomad4 SAS exome

AF:

0.0503

Gnomad4 FIN exome

AF:

0.0381

Gnomad4 NFE exome

AF:

0.0473

Gnomad4 OTH exome

AF:

0.0445

GnomAD4 genome

AF:

0.000379

AC:

AN:

145184

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

70508

show subpopulations

Gnomad4 AFR

AF:

0.000679

Gnomad4 AMR

AF:

0.000137

Gnomad4 ASJ

AF:

0.000296

Gnomad4 EAS

AF:

0.000199

Gnomad4 SAS

AF:

0.000219

Gnomad4 FIN

AF:

0.00111

Gnomad4 NFE

AF:

0.000152

Gnomad4 OTH

AF:

0.00150

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jun 27, 2022

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Welander distal myopathy

Benign:1

Jan 09, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

2-70229320-TAAAAA-TAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over