chr7-31553124-C-A

Variant names:

• chr7-31553124-C-A
• NM_001257967.3:c.100C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001257967.3(ITPRID1):​c.100C>A​(p.Leu34Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,444,490 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ITPRID1 NM_001257967.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.400
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24733841).

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.100C>A	p.Leu34Met	missense	Exon 3 of 15	NP_001244896.2	Q6ZRS4-1
	ITPRID1	NM_194300.5		c.100C>A	p.Leu34Met	missense	Exon 2 of 14	NP_919276.2	Q6ZRS4-1
	ITPRID1	NM_001257968.3		c.100C>A	p.Leu34Met	missense	Exon 2 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.100C>A	p.Leu34Met	missense	Exon 3 of 15	ENSP00000478518.2	Q6ZRS4-1
	ITPRID1	ENST00000407970.7	TSL:1	c.100C>A	p.Leu34Met	missense	Exon 2 of 14	ENSP00000384416.3	Q6ZRS4-1
	ITPRID1	ENST00000888409.1		c.100C>A	p.Leu34Met	missense	Exon 2 of 14	ENSP00000558468.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1444490 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 716624

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33168

American (AMR) AF: 0.00 AC: 0 AN: 42608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25762

East Asian (EAS) AF: 0.00 AC: 0 AN: 38916

South Asian (SAS) AF: 0.00 AC: 0 AN: 83188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1102902

Other (OTH) AF: 0.00 AC: 0 AN: 59840

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000203476), which strongly suggests a high chance of mosaicism in these individuals.

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	0.12
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T
Eigen	Benign	0.055
Eigen_PC	Benign	-0.055
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.83	T
PhyloP100		0.40
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.25
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.050	T
Polyphen		1.0	D
Vest4		0.16
MutPred		0.16		Gain of catalytic residue at L34 (P = 0.007)
MVP		0.26
MPC		0.19
ClinPred		0.93	D
GERP RS		4.5
Varity_R		0.088
gMVP		0.076
Mutation Taster		=92/8	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

hg19: chr7-31592738;