NM_001257967.3:c.686C>G

Variant names:

• chr7-31577950-C-G
• rs752868206
• NM_001257967.3:c.686C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001257967.3(ITPRID1):​c.686C>G​(p.Ala229Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ITPRID1 NM_001257967.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.155
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053094923).

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.686C>G	p.Ala229Gly	missense	Exon 9 of 15	NP_001244896.2	Q6ZRS4-1
	ITPRID1	NM_194300.5		c.686C>G	p.Ala229Gly	missense	Exon 8 of 14	NP_919276.2	Q6ZRS4-1
	ITPRID1	NM_001257968.3		c.686C>G	p.Ala229Gly	missense	Exon 8 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.686C>G	p.Ala229Gly	missense	Exon 9 of 15	ENSP00000478518.2	Q6ZRS4-1
	ITPRID1	ENST00000407970.7	TSL:1	c.686C>G	p.Ala229Gly	missense	Exon 8 of 14	ENSP00000384416.3	Q6ZRS4-1
	ITPRID1	ENST00000888409.1		c.686C>G	p.Ala229Gly	missense	Exon 8 of 14	ENSP00000558468.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000240 AC: 6 AN: 250022 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461412 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 726964

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39654

South Asian (SAS) AF: 0.00 AC: 0 AN: 86202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111768

Other (OTH) AF: 0.0000166 AC: 1 AN: 60366

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

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	0.10
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.1
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.15
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.014
Sift	Benign	0.20	T
Sift4G	Benign	0.28	T
Polyphen		0.041	B
Vest4		0.062
MutPred		0.18		Loss of helix (P = 0.0068)
MVP		0.17
MPC		0.035
ClinPred		0.064	T
GERP RS		0.71
Varity_R		0.045
gMVP		0.12
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: rs752868206; hg19: chr7-31617564;