NM_001257967.3:c.227A>C

Variant names:

• chr7-31554872-A-C
• rs1462103126
• NM_001257967.3:c.227A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001257967.3(ITPRID1):​c.227A>C​(p.Glu76Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ITPRID1 NM_001257967.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.73
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29011503).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257967.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPRID1	NM_001257967.3	MANE Select	c.227A>C	p.Glu76Ala	missense	Exon 5 of 15	NP_001244896.2	Q6ZRS4-1
	ITPRID1	NM_194300.5		c.227A>C	p.Glu76Ala	missense	Exon 4 of 14	NP_919276.2	Q6ZRS4-1
	ITPRID1	NM_001257968.3		c.227A>C	p.Glu76Ala	missense	Exon 4 of 15	NP_001244897.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPRID1	ENST00000615280.5	TSL:2 MANE Select	c.227A>C	p.Glu76Ala	missense	Exon 5 of 15	ENSP00000478518.2	Q6ZRS4-1
	ITPRID1	ENST00000407970.7	TSL:1	c.227A>C	p.Glu76Ala	missense	Exon 4 of 14	ENSP00000384416.3	Q6ZRS4-1
	ITPRID1	ENST00000888409.1		c.227A>C	p.Glu76Ala	missense	Exon 4 of 14	ENSP00000558468.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0034	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.50	T
PhyloP100		1.7
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.11
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.26
MutPred		0.27		Gain of helix (P = 0.062)
MVP		0.69
MPC		0.23
ClinPred		0.99	D
GERP RS		5.1
PromoterAI		-0.013	Neutral
Varity_R		0.16
gMVP		0.095
Mutation Taster		=76/24	polymorphism

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: rs1462103126; hg19: chr7-31594486;