rs201794126

Variant names:

• chr16-19115438-C-G
• rs201794126
• NM_001034841.4:c.977C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-19115438-C-G
• chr16-19115438-C-T

Variant summary

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

The NM_001034841.4(ITPRIPL2):​c.977C>G​(p.Pro326Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P326L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ITPRIPL2 NM_001034841.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.246
• Publications: 1 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: 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=0.13173544).

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.977C>G	p.Pro326Arg	missense	Exon 1 of 1	NP_001030013.1	Q3MIP1
	ITPRIPL2	NR_028028.2		n.959C>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.977C>G	p.Pro326Arg	missense	Exon 1 of 1	ENSP00000370849.3	Q3MIP1
	ITPRIPL2	ENST00000566735.1	TSL:2	n.991C>G		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000261427	ENST00000564808.6	TSL:4	n.418+503C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247576 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458008 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725512

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49656

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111956

Other (OTH) AF: 0.00 AC: 0 AN: 60358

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.25
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.075
Sift	Benign	0.58	T
Sift4G	Benign	0.64	T
Polyphen		0.80	P
Vest4		0.33
MutPred		0.56		Loss of glycosylation at P326 (P = 5e-04)
MVP		0.14
ClinPred		0.097	T
GERP RS		1.3
Varity_R		0.031
gMVP		0.77

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: rs201794126; hg19: chr16-19126760;