chr2-96327349-C-G

Position:

• chr2-96327349-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001008949.3(ITPRIPL1):​c.718C>G​(p.Pro240Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 5.26

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.93

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPRIPL1	NM_001008949.3	c.718C>G	p.Pro240Ala	missense_variant	3/3	ENST00000439118.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPRIPL1	ENST00000439118.3	c.718C>G	p.Pro240Ala	missense_variant	3/3	1	NM_001008949.3
ITPRIPL1	ENST00000420728.1	c.814C>G	p.Pro272Ala	missense_variant	2/2	2
ITPRIPL1	ENST00000361124.5	c.742C>G	p.Pro248Ala	missense_variant	1/1
ITPRIPL1	ENST00000536814.1	c.694C>G	p.Pro232Ala	missense_variant	2/2	3		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

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

Jul 20, 2022

The c.742C>G (p.P248A) alteration is located in exon 1 (coding exon 1) of the ITPRIPL1 gene. This alteration results from a C to G substitution at nucleotide position 742, causing the proline (P) at amino acid position 248 to be replaced by an alanine (A). 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	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	.;T;.
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.79	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Pathogenic	0.93	D;D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.5	.;M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-6.9	D;D;D
REVEL	Uncertain	0.47
Sift	Uncertain	0.012	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.61
MutPred		0.93		.;Gain of catalytic residue at P240 (P = 0.2388);.;
MVP		0.63
MPC		0.63
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.35
gMVP		0.65

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: chr2-96993087;