16-19115452-A-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S331C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ITPRIPL2 NM_001034841.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034841.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPRIPL2	NM_001034841.4	MANE Select	c.991A>G	p.Ser331Gly	missense	Exon 1 of 1	NP_001030013.1	Q3MIP1
	ITPRIPL2	NR_028028.2		n.973A>G		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPRIPL2	ENST00000381440.5	TSL:6 MANE Select	c.991A>G	p.Ser331Gly	missense	Exon 1 of 1	ENSP00000370849.3	Q3MIP1
	ITPRIPL2	ENST00000566735.1	TSL:2	n.1005A>G		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000261427	ENST00000564808.6	TSL:4	n.418+517A>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-0.14
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

Other links and lift over

dbSNP: rs370538130; hg19: chr16-19126774;