chr2-96327115-T-G

Position:

• chr2-96327115-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001008949.3(ITPRIPL1):​c.484T>G​(p.Phe162Val) 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. 12/21 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)
• Consequence: ITPRIPL1 NM_001008949.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.623

Genes affected

ITPRIPL1 (HGNC:29371): (ITPRIP like 1) Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10133979).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPRIPL1	NM_001008949.3	c.484T>G	p.Phe162Val	missense_variant	3/3	ENST00000439118.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPRIPL1	ENST00000439118.3	c.484T>G	p.Phe162Val	missense_variant	3/3	1	NM_001008949.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2024

The c.508T>G (p.F170V) alteration is located in exon 1 (coding exon 1) of the ITPRIPL1 gene. This alteration results from a T to G substitution at nucleotide position 508, causing the phenylalanine (F) at amino acid position 170 to be replaced by a valine (V). 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	0.29
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0071	.;.;T;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.58	T;T;T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.10	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	.;.;M;.
MutationTaster	Benign	0.99	N;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.7	D;N;N;N
REVEL	Benign	0.075
Sift	Benign	0.25	T;T;T;T
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.063, 0.10	.;.;B;B
Vest4		0.28, 0.29, 0.22
MutPred		0.36		.;.;Gain of catalytic residue at F162 (P = 0.0623);.;
MVP		0.24
MPC		0.19
ClinPred		0.60	D
GERP RS		2.5
Varity_R		0.051
gMVP		0.51

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-96992853;