rs79075815

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-70214459-C-A
• chr2-70214459-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022173.4(TIA1):​c.924G>T​(p.Gln308His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,398 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q308Q) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TIA1 NM_022173.4 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>T	p.Gln308His	missense	Exon 12 of 13	NP_071505.2
	TIA1	NM_001351508.2		c.921G>T	p.Gln307His	missense	Exon 12 of 13	NP_001338437.1
	TIA1	NM_001351509.2		c.897G>T	p.Gln299His	missense	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>T	p.Gln308His	missense	Exon 12 of 13	ENSP00000401371.2
	TIA1	ENST00000415783.6	TSL:1	c.891G>T	p.Gln297His	missense	Exon 11 of 12	ENSP00000404023.2
	TIA1	ENST00000282574.8	TSL:5	c.921G>T	p.Gln307His	missense	Exon 12 of 13	ENSP00000282574.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461398 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726966

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 86118

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111866

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.035
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.3
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.28
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.031	D
Polyphen		0.011	B
Vest4		0.78
MutPred		0.41		Loss of MoRF binding (P = 0.0915)
MVP		0.94
MPC		1.4
ClinPred		0.85	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.76
Mutation Taster		=46/54	disease causing

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

Other links and lift over

dbSNP: rs79075815; hg19: chr2-70441591;