7-31574686-G-T

Variant names:

• chr7-31574686-G-T
• NM_001257967.3:c.542G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001257967.3(ITPRID1):​c.542G>T​(p.Arg181Leu) 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. 12/20 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)
• Consequence: ITPRID1 NM_001257967.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0670

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3132186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPRID1	NM_001257967.3	c.542G>T	p.Arg181Leu	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.542G>T	p.Arg181Leu	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

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.542G>T (p.R181L) alteration is located in exon 7 (coding exon 6) of the CCDC129 gene. This alteration results from a G to T substitution at nucleotide position 542, causing the arginine (R) at amino acid position 181 to be replaced by a leucine (L). 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	0.19
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	6.0
DANN	Uncertain	1.0
DEOGEN2	Benign	0.082	.;.;T;.;.
Eigen	Benign	-0.066
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.30	N
LIST_S2	Uncertain	0.93	D;D;D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.31	T;T;T;T;T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.21	T
PROVEAN	Pathogenic	-4.6	.;D;D;D;D
REVEL	Benign	0.13
Sift	Uncertain	0.015	.;D;D;D;D
Sift4G	Uncertain	0.047	D;T;D;D;D
Polyphen		0.99	.;D;D;.;.
Vest4		0.52
MutPred		0.43		.;Loss of MoRF binding (P = 0.0635);Loss of MoRF binding (P = 0.0635);.;.;
MVP		0.17
MPC		0.18
ClinPred		0.98	D
GERP RS		-0.70
Varity_R		0.25
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-31614300;