Variant 5-157460331-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001099287.2(NIPAL4):c.11G>C(p.Arg4Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,395,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NIPAL4
NM_001099287.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.691

Variant links:

Genes affected

NIPAL4 (HGNC:28018): (NIPA like domain containing 4) This gene likely encodes a membrane receptor. Mutations in this gene have been associated with autosomal recessive congenital ichthyosis. [provided by RefSeq, Feb 2010]

NIPAL4 links:

ADAM19 (HGNC:197): (ADAM metallopeptidase domain 19) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. This member is a type I transmembrane protein and serves as a marker for dendritic cell differentiation. It has been demonstrated to be an active metalloproteinase, which may be involved in normal physiological processes such as cell migration, cell adhesion, cell-cell and cell-matrix interactions, and signal transduction. It is proposed to play a role in pathological processes, such as cancer, inflammatory diseases, renal diseases, and Alzheimer's disease. [provided by RefSeq, May 2013]

ADAM19 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.07876223).

BP6

Variant 5-157460331-G-C is Benign according to our data. Variant chr5-157460331-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2624350.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIPAL4	NM_001099287.2 linkuse as main transcript	c.11G>C	p.Arg4Pro	missense_variant	1/6	ENST00000311946.8	NP_001092757.2
NIPAL4	NM_001172292.2 linkuse as main transcript	c.11G>C	p.Arg4Pro	missense_variant	1/5		NP_001165763.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NIPAL4	ENST00000311946.8 linkuse as main transcript	c.11G>C	p.Arg4Pro	missense_variant	1/6	1	NM_001099287.2	ENSP00000311687	P1	Q0D2K0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000211

AC:

AN:

141990

Hom.:

AF XY:

0.0000130

AC XY:

AN XY:

76838

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000190

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000240

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1395418

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

688090

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000561

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.032

.;T

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.53

T;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.079

T;T

MetaSVM

Benign

-0.52

MutationAssessor

Benign

-0.14

N;N

MutationTaster

Benign

0.99

D;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.89

N;N

REVEL

Benign

0.25

Sift

Benign

0.17

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.0

B;B

Vest4

0.099

MutPred

0.35

Gain of glycosylation at S68 (P = 0.0351);Gain of glycosylation at S68 (P = 0.0351);

MVP

0.32

MPC

0.39

ClinPred

0.14

GERP RS

-0.60

Varity_R

0.26

gMVP

0.28

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over