NM_001008949.3:c.367G>A

Variant names:

• chr2-96326998-G-A
• rs376725131
• NM_001008949.3:c.367G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001008949.3(ITPRIPL1):​c.367G>A​(p.Val123Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000165 in 1,614,026 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: ITPRIPL1 NM_001008949.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.182
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.025431335).
• BP6: Variant 2-96326998-G-A is Benign according to our data. Variant chr2-96326998-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3530987.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPRIPL1	NM_001008949.3	MANE Select	c.367G>A	p.Val123Ile	missense	Exon 3 of 3	NP_001008949.1	Q6GPH6-1
	ITPRIPL1	NM_178495.6		c.391G>A	p.Val131Ile	missense	Exon 1 of 1	NP_848590.3
	ITPRIPL1	NM_001163523.2		c.343G>A	p.Val115Ile	missense	Exon 2 of 2	NP_001156995.1	Q6GPH6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPRIPL1	ENST00000439118.3	TSL:1 MANE Select	c.367G>A	p.Val123Ile	missense	Exon 3 of 3	ENSP00000389308.2	Q6GPH6-1
	ITPRIPL1	ENST00000420728.1	TSL:2	c.460G>A	p.Val154Ile	missense	Exon 2 of 2	ENSP00000396552.1	H7C0T2
	ITPRIPL1	ENST00000361124.5	TSL:6	c.391G>A	p.Val131Ile	missense	Exon 1 of 1	ENSP00000355121.4	Q6GPH6-2

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152144 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000756 AC: 19 AN: 251488 AF XY: 0.0000883

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000174 AC: 254 AN: 1461882 Hom.: 0 Cov.: 34 AF XY: 0.000165 AC XY: 120 AN XY: 727242

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000215 AC: 239 AN: 1112006

Other (OTH) AF: 0.000166 AC: 10 AN: 60392

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152144 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74320

African (AFR) AF: 0.000121 AC: 5 AN: 41438

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000115 Hom.: 0

Bravo AF: 0.0000869

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000576 AC: 7

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.060
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.1
DANN	Benign	0.69
DEOGEN2	Benign	0.0080	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.57	N
PhyloP100		-0.18
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.041
Sift	Benign	0.94	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.022
MVP		0.088
MPC		0.12
ClinPred		0.014	T
GERP RS		0.10
Varity_R		0.012
gMVP		0.063
Mutation Taster		=99/1	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: rs376725131; hg19: chr2-96992736;