Variant chr5-157460262-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001099287.2(NIPAL4):c.-59C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000908 in 1,541,336 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00080 ( 13 hom. )

Consequence

NIPAL4
NM_001099287.2 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.419

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023286939).

BP6

Variant 5-157460262-C-T is Benign according to our data. Variant chr5-157460262-C-T is described in ClinVar as [Benign]. Clinvar id is 1669807.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIPAL4	NM_001099287.2 linkuse as main transcript	c.-59C>T		5_prime_UTR_variant	1/6	ENST00000311946.8	NP_001092757.2
NIPAL4	NM_001172292.2 linkuse as main transcript	c.-59C>T		5_prime_UTR_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.-59C>T		5_prime_UTR_variant	1/6	1	NM_001099287.2	ENSP00000311687	P1	Q0D2K0-1

Frequencies

GnomAD3 genomes

AF:

0.00188

AC:

286

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0250

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00220

AC:

298

AN:

135222

Hom.:

AF XY:

0.00192

AC XY:

142

AN XY:

73872

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0189

Gnomad NFE exome

AF:

0.000146

Gnomad OTH exome

AF:

0.00153

GnomAD4 exome

AF:

0.000801

AC:

1113

AN:

1388990

Hom.:

Cov.:

AF XY:

0.000799

AC XY:

547

AN XY:

684660

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0200

Gnomad4 NFE exome

AF:

0.0000986

Gnomad4 OTH exome

AF:

0.000922

GnomAD4 genome

AF:

0.00188

AC:

286

AN:

152346

Hom.:

Cov.:

AF XY:

0.00270

AC XY:

201

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0250

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000449

Hom.:

Bravo

AF:

0.000110

ExAC

AF:

0.000826

AC:

Asia WGS

AF:

0.000867

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 08, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.045

.;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.60

T;T

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-0.55

MutationAssessor

Benign

0.81

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.19

Sift

Uncertain

0.011

D;D

Sift4G

Uncertain

0.019

D;D

Polyphen

0.0010

B;B

Vest4

0.16

MVP

0.19

MPC

0.29

ClinPred

0.11

GERP RS

0.45

Varity_R

0.058

gMVP

0.12

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