rs193921120

Variant names:

• chr2-96327946-G-A
• rs193921120
• NM_001008949.3:c.1315G>A

Variant summary

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

The NM_001008949.3(ITPRIPL1):​c.1315G>A​(p.Ala439Thr) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITPRIPL1 NM_001008949.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.65
• Publications: 0 publications found

Genes affected

ITPRIPL1 (HGNC:29371): (ITPRIP like 1) Located in membrane. [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=0.082819134).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008949.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPRIPL1	NM_001008949.3	MANE Select	c.1315G>A	p.Ala439Thr	missense	Exon 3 of 3	NP_001008949.1
	ITPRIPL1	NM_178495.6		c.1339G>A	p.Ala447Thr	missense	Exon 1 of 1	NP_848590.3
	ITPRIPL1	NM_001163523.2		c.1291G>A	p.Ala431Thr	missense	Exon 2 of 2	NP_001156995.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPRIPL1	ENST00000439118.3	TSL:1 MANE Select	c.1315G>A	p.Ala439Thr	missense	Exon 3 of 3	ENSP00000389308.2
	ITPRIPL1	ENST00000420728.1	TSL:2	c.1408G>A	p.Ala470Thr	missense	Exon 2 of 2	ENSP00000396552.1
	ITPRIPL1	ENST00000361124.5	TSL:6	c.1339G>A	p.Ala447Thr	missense	Exon 1 of 1	ENSP00000355121.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Prostate cancer Uncertain:1

Science for Life laboratory, Karolinska Institutet

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.0014	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.6
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.080	N
REVEL	Benign	0.035
Sift	Benign	0.069	T
Sift4G	Benign	0.23	T
Polyphen		0.46	P
Vest4		0.25
MutPred		0.20		Gain of glycosylation at A439 (P = 0.0297)
MVP		0.24
MPC		0.22
ClinPred		0.10	T
GERP RS		2.4
Varity_R		0.034
gMVP		0.093
Mutation Taster		=94/6	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

dbSNP: rs193921120; hg19: chr2-96993684; COSMIC: COSV63152933; COSMIC: COSV63152933;