16-19115452-A-G

Variant names:

• chr16-19115452-A-G
• rs370538130
• NM_001034841.4:c.991A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001034841.4(ITPRIPL2):​c.991A>G​(p.Ser331Gly) 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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ITPRIPL2 NM_001034841.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136

Genes affected

ITPRIPL2 (HGNC:27257): (ITPRIP like 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000261427 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046470553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPRIPL2	NM_001034841.4	c.991A>G	p.Ser331Gly	missense_variant	Exon 1 of 1	ENST00000381440.5	NP_001030013.1
ITPRIPL2	NR_028028.2	n.973A>G		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPRIPL2	ENST00000381440.5	c.991A>G	p.Ser331Gly	missense_variant	Exon 1 of 1	6	NM_001034841.4	ENSP00000370849.3
ITPRIPL2	ENST00000566735.1	n.1005A>G		non_coding_transcript_exon_variant	Exon 2 of 2	2
ENSG00000261427	ENST00000564808.6	n.418+517A>G		intron_variant	Intron 2 of 5	4
ENSG00000261427	ENST00000568526.1	n.211+667A>G		intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.85
DANN	Benign	0.60
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.011
Sift	Benign	0.45	T
Sift4G	Benign	0.52	T
Polyphen		0.0	B
Vest4		0.092
MutPred		0.29		Loss of glycosylation at S331 (P = 0.0083);
MVP		0.030
ClinPred		0.034	T
GERP RS		-0.45
Varity_R		0.034
gMVP		0.24

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

LitVar

Other links and lift over

dbSNP: rs370538130; hg19: chr16-19126774;