Variant 8-98294038-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000430223.7(NIPAL2):c.100G>T(p.Gly34Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,497,232 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G34D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

NIPAL2
ENST00000430223.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.15

Variant links:

Genes affected

NIPAL2 (HGNC:25854): (NIPA like domain containing 2) Predicted to enable magnesium ion transmembrane transporter activity. Predicted to be involved in magnesium ion transport. Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

NIPAL2 links:

LOC105375659 (HGNC:):

LOC105375659 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIPAL2	NM_001321635.2 linkuse as main transcript	c.100G>T	p.Gly34Cys	missense_variant	1/11	ENST00000430223.7	NP_001308564.1
LOC105375659	XR_007061023.1 linkuse as main transcript	n.742+6170C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NIPAL2	ENST00000430223.7 linkuse as main transcript	c.100G>T	p.Gly34Cys	missense_variant	1/11	1	NM_001321635.2	ENSP00000407087	P1	Q9H841-2
NIPAL2	ENST00000341166.3 linkuse as main transcript	c.100G>T	p.Gly34Cys	missense_variant	1/12	2		ENSP00000339256		Q9H841-1
NIPAL2	ENST00000519324.1 linkuse as main transcript	n.73G>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000112

AC:

AN:

1345114

Hom.:

Cov.:

AF XY:

0.00000905

AC XY:

AN XY:

662940

show subpopulations

Gnomad4 AFR exome

AF:

0.000516

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000180

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000117

ExAC

AF:

0.0000251

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 04, 2024

The c.100G>T (p.G34C) alteration is located in exon 1 (coding exon 1) of the NIPAL2 gene. This alteration results from a G to T substitution at nucleotide position 100, causing the glycine (G) at amino acid position 34 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

.;T

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.71

T;T

M_CAP

Pathogenic

0.97

MetaRNN

Uncertain

0.58

D;D

MetaSVM

Uncertain

0.73

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

0.58

D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.8

N;N

REVEL

Uncertain

0.59

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.016

D;D

Polyphen

1.0

.;D

Vest4

0.41

MVP

0.78

MPC

0.65

ClinPred

0.97

GERP RS

4.5

Varity_R

0.38

gMVP

0.52

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