7-31574637-C-G

Variant names:

• chr7-31574637-C-G
• rs757614338
• NM_001257967.3:c.493C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001257967.3(ITPRID1):​c.493C>G​(p.Pro165Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITPRID1 NM_001257967.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.31

Genes affected

ITPRID1 (HGNC:27363): (ITPR interacting domain containing 1) Predicted to enable signaling receptor binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.938

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPRID1	NM_001257967.3	c.493C>G	p.Pro165Ala	missense_variant	Exon 8 of 15	ENST00000615280.5	NP_001244896.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPRID1	ENST00000615280.5	c.493C>G	p.Pro165Ala	missense_variant	Exon 8 of 15	2	NM_001257967.3	ENSP00000478518.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	.;.;.;T;.;.
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T;T;T;T;T;T
M_CAP	Benign	0.074	D
MetaRNN	Pathogenic	0.94	D;D;D;D;D;D
MetaSVM	Uncertain	0.13	D
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-7.7	.;D;D;D;D;D
REVEL	Pathogenic	0.75
Sift	Pathogenic	0.0	.;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		1.0	.;.;D;D;.;.
Vest4		0.66
MVP		0.92
MPC		0.23
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.81
gMVP		0.80

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

Other links and lift over

dbSNP: rs757614338; hg19: chr7-31614251;