2-70214459-C-T

Variant names:

• chr2-70214459-C-T
• rs79075815
• NM_022173.4:c.924G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_022173.4(TIA1):​c.924G>A​(p.Gln308Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000666 in 1,613,666 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00037 (3 hom.)
• Consequence: TIA1 NM_022173.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.28
• Publications: 2 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 2-70214459-C-T is Benign according to our data. Variant chr2-70214459-C-T is described in ClinVar as Benign. ClinVar VariationId is 458842.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.28 with no splicing effect.
• BS2: High AC in GnomAd4 at 531 AD,Unknown gene.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIA1	NM_022173.4	MANE Select	c.924G>A	p.Gln308Gln	synonymous	Exon 12 of 13	NP_071505.2
	TIA1	NM_001351508.2		c.921G>A	p.Gln307Gln	synonymous	Exon 12 of 13	NP_001338437.1
	TIA1	NM_001351509.2		c.897G>A	p.Gln299Gln	synonymous	Exon 11 of 12	NP_001338438.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIA1	ENST00000433529.7	TSL:2 MANE Select	c.924G>A	p.Gln308Gln	synonymous	Exon 12 of 13	ENSP00000401371.2
	TIA1	ENST00000415783.6	TSL:1	c.891G>A	p.Gln297Gln	synonymous	Exon 11 of 12	ENSP00000404023.2
	TIA1	ENST00000881363.1		c.1020G>A	p.Gln340Gln	synonymous	Exon 13 of 14	ENSP00000551422.1

Frequencies

GnomAD3 genomes AF: 0.00349 AC: 531 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000857 AC: 215 AN: 250816 AF XY: 0.000635

Gnomad AFR exome AF: 0.0120

Gnomad AMR exome AF: 0.000261

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: 0.000327

GnomAD4 exome AF: 0.000372 AC: 544 AN: 1461396 Hom.: 3 Cov.: 31 AF XY: 0.000347 AC XY: 252 AN XY: 726966

African (AFR) AF: 0.0126 AC: 422 AN: 33462

American (AMR) AF: 0.000314 AC: 14 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00174 AC: 10 AN: 5744

European-Non Finnish (NFE) AF: 0.0000369 AC: 41 AN: 1111866

Other (OTH) AF: 0.000927 AC: 56 AN: 60380

GnomAD4 genome AF: 0.00349 AC: 531 AN: 152270 Hom.: 0 Cov.: 32 AF XY: 0.00351 AC XY: 261 AN XY: 74456

African (AFR) AF: 0.0123 AC: 510 AN: 41546

American (AMR) AF: 0.000654 AC: 10 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68024

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00174 Hom.: 0

Bravo AF: 0.00389

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Welander distal myopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	6.7
DANN	Benign	0.82
PhyloP100		2.3
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs79075815; hg19: chr2-70441591;