NM_001099287.2:c.92A>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001099287.2(NIPAL4):c.92A>G(p.Asn31Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000835 in 1,613,980 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0045 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00045 ( 5 hom. )

Consequence

NIPAL4
NM_001099287.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.30

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028746426).

BP6

Variant 5-157463148-A-G is Benign according to our data. Variant chr5-157463148-A-G is described in ClinVar as [Benign]. Clinvar id is 776087.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00449 (683/152278) while in subpopulation AFR AF= 0.0156 (648/41550). AF 95% confidence interval is 0.0146. There are 5 homozygotes in gnomad4. There are 320 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPAL4	NM_001099287.2 link	c.92A>G	p.Asn31Ser	missense_variant	Exon 2 of 6	ENST00000311946.8	NP_001092757.2	Q0D2K0-1
NIPAL4	NM_001172292.2 link	c.92A>G	p.Asn31Ser	missense_variant	Exon 2 of 5		NP_001165763.2	Q0D2K0-2
NIPAL4	XM_011534552.2 link	c.-218A>G		5_prime_UTR_variant	Exon 2 of 6		XP_011532854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIPAL4	ENST00000311946.8 link	c.92A>G	p.Asn31Ser	missense_variant	Exon 2 of 6	1	NM_001099287.2	ENSP00000311687.8		Q0D2K0-1

Frequencies

GnomAD3 genomes

AF:

0.00450

AC:

684

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0156

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00115

AC:

286

AN:

249256

Hom.:

AF XY:

0.000932

AC XY:

126

AN XY:

135222

show subpopulations

Gnomad AFR exome

AF:

0.0169

Gnomad AMR exome

AF:

0.000608

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000496

GnomAD4 exome

AF:

0.000455

AC:

665

AN:

1461702

Hom.:

Cov.:

AF XY:

0.000411

AC XY:

299

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.0173

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.000696

GnomAD4 genome

AF:

0.00449

AC:

683

AN:

152278

Hom.:

Cov.:

AF XY:

0.00430

AC XY:

320

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0156

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000759

Hom.:

Bravo

AF:

0.00502

ESP6500AA

AF:

0.0180

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.00139

AC:

168

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 11, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Benign

1.9

DANN

Benign

0.66

DEOGEN2

Benign

0.032

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0064

LIST_S2

Benign

0.21

T;T

MetaRNN

Benign

0.0029

T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

-0.55

N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

0.39

N;N

REVEL

Benign

0.20

Sift

Benign

0.58

T;T

Sift4G

Benign

0.48

T;T

Polyphen

0.0

B;B

Vest4

0.076

MVP

0.17

MPC

0.22

ClinPred

0.0096

GERP RS

3.4

Varity_R

0.027

gMVP

0.22

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