Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_022173.4(TIA1):c.223-5_223-3delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000925 in 1,080,550 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: not found (cov: 30)

Exomes 𝑓: 9.3e-7 ( 0 hom. )

Consequence

TIA1
NM_022173.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.549

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 2-70229320-TAAA-T is Benign according to our data. Variant chr2-70229320-TAAA-T is described in ClinVar as Benign. ClinVar VariationId is 2150473.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022173.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TIA1	NM_022173.4	MANE Select	c.223-5_223-3delTTT	splice_region intron	N/A	NP_071505.2
TIA1	NM_001351508.2		c.223-5_223-3delTTT	splice_region intron	N/A	NP_001338437.1
TIA1	NM_001351509.2		c.229-5_229-3delTTT	splice_region intron	N/A	NP_001338438.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TIA1	ENST00000433529.7	TSL:2 MANE Select	c.223-5_223-3delTTT	splice_region intron	N/A	ENSP00000401371.2
TIA1	ENST00000415783.6	TSL:1	c.223-5_223-3delTTT	splice_region intron	N/A	ENSP00000404023.2
TIA1	ENST00000416149.6	TSL:1	c.223-5_223-3delTTT	splice_region intron	N/A	ENSP00000413751.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

100452

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.25e-7

AC:

AN:

1080550

Hom.:

AF XY:

0.00

AC XY:

AN XY:

537750

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24018

American (AMR)

AF:

0.00

AC:

AN:

30864

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18798

East Asian (EAS)

AF:

0.00

AC:

AN:

29690

South Asian (SAS)

AF:

0.00

AC:

AN:

62022

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4224

European-Non Finnish (NFE)

AF:

0.00000121

AC:

AN:

827430

Other (OTH)

AF:

0.00

AC:

AN:

44088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Welander distal myopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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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2-70229320-TAAAAA-TAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over