rs752868206

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 13/20 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

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 Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPRID1	NM_001257967.3	c.686C>G	p.Ala229Gly	missense_variant	Exon 9 of 15	ENST00000615280.5	NP_001244896.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPRID1	ENST00000615280.5	c.686C>G	p.Ala229Gly	missense_variant	Exon 9 of 15	2	NM_001257967.3	ENSP00000478518.2
ITPRID1	ENST00000407970.7	c.686C>G	p.Ala229Gly	missense_variant	Exon 8 of 14	1		ENSP00000384416.3
ITPRID1	ENST00000409210.1	c.410C>G	p.Ala137Gly	missense_variant	Exon 6 of 13	2		ENSP00000387214.1
ITPRID1	ENST00000319386.7	c.686C>G	p.Ala229Gly	missense_variant	Exon 8 of 14	2		ENSP00000313062.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000240 AC: 6 AN: 250022 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135072

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 SAS exome AF: 0.00

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.686C>G (p.A229G) alteration is located in exon 8 (coding exon 7) of the CCDC129 gene. This alteration results from a C to G substitution at nucleotide position 686, causing the alanine (A) at amino acid position 229 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;T;T;T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.053	T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.3	.;N;N;N;N
REVEL	Benign	0.014
Sift	Benign	0.20	.;T;T;T;T
Sift4G	Benign	0.28	T;T;T;T;T
Polyphen		0.041	.;B;B;.;.
Vest4		0.062
MutPred		0.18		.;Loss of helix (P = 0.0068);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

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

Publications

LitVar

Other links and lift over

dbSNP: rs752868206; hg19: chr7-31617564;