7-31554872-A-T

Variant names:

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

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>T​(p.Glu76Val) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E76A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ITPRID1 NM_001257967.3 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.34500325).

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>T	p.Glu76Val	missense	Exon 5 of 15	NP_001244896.2	Q6ZRS4-1
	ITPRID1	NM_194300.5		c.227A>T	p.Glu76Val	missense	Exon 4 of 14	NP_919276.2	Q6ZRS4-1
	ITPRID1	NM_001257968.3		c.227A>T	p.Glu76Val	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>T	p.Glu76Val	missense	Exon 5 of 15	ENSP00000478518.2	Q6ZRS4-1
	ITPRID1	ENST00000407970.7	TSL:1	c.227A>T	p.Glu76Val	missense	Exon 4 of 14	ENSP00000384416.3	Q6ZRS4-1
	ITPRID1	ENST00000888409.1		c.227A>T	p.Glu76Val	missense	Exon 4 of 14	ENSP00000558468.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 205714 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 Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.0082	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.053	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.35	T
MetaSVM	Uncertain	-0.25	T
PhyloP100		1.7
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Benign	0.19
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.31
MutPred		0.36		Gain of sheet (P = 0.0827)
MVP		0.67
MPC		0.24
ClinPred		0.97	D
GERP RS		5.1
PromoterAI		-0.025	Neutral
Varity_R		0.23
gMVP		0.15
Mutation Taster		=73/27	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;