chr2-96327648-T-G

Position:

• chr2-96327648-T-G

Variant summary

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

The NM_001008949.3(ITPRIPL1):​c.1017T>G​(p.Phe339Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITPRIPL1 NM_001008949.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.108

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPRIPL1	NM_001008949.3	c.1017T>G	p.Phe339Leu	missense_variant	3/3	ENST00000439118.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPRIPL1	ENST00000439118.3	c.1017T>G	p.Phe339Leu	missense_variant	3/3	1	NM_001008949.3
ITPRIPL1	ENST00000420728.1	c.1113T>G	p.Phe371Leu	missense_variant	2/2	2
ITPRIPL1	ENST00000361124.5	c.1041T>G	p.Phe347Leu	missense_variant	1/1
ITPRIPL1	ENST00000536814.1	c.993T>G	p.Phe331Leu	missense_variant	2/2	3		P1

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

Apr 08, 2022

The c.1041T>G (p.F347L) 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 1041, causing the phenylalanine (F) at amino acid position 347 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	Pathogenic	0.96
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.097	.;T;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.46
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.73	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.56	D;D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.4	.;M;.
MutationTaster	Benign	0.55	D;D;D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Benign	0.12
Sift	Benign	0.10	T;T;T
Sift4G	Benign	0.51	T;T;T
Polyphen		0.78, 0.86	.;P;P
Vest4		0.68
MutPred		0.58		.;Loss of catalytic residue at F339 (P = 0.0131);.;
MVP		0.15
MPC		0.68
ClinPred		0.92	D
GERP RS		-2.7
Varity_R		0.15
gMVP		0.35

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: chr2-96993386;