Variant 8-98294037-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001321635.2(NIPAL2):c.101G>A(p.Gly34Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NIPAL2
NM_001321635.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.53

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40119535).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIPAL2	NM_001321635.2 linkuse as main transcript	c.101G>A	p.Gly34Asp	missense_variant	1/11	ENST00000430223.7	NP_001308564.1
LOC105375659	XR_007061023.1 linkuse as main transcript	n.742+6169C>T		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.101G>A	p.Gly34Asp	missense_variant	1/11	1	NM_001321635.2	ENSP00000407087	P1	Q9H841-2
NIPAL2	ENST00000341166.3 linkuse as main transcript	c.101G>A	p.Gly34Asp	missense_variant	1/12	2		ENSP00000339256		Q9H841-1
NIPAL2	ENST00000519324.1 linkuse as main transcript	n.74G>A		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1344972

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

662828

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jul 13, 2021

The c.101G>A (p.G34D) alteration is located in exon 1 (coding exon 1) of the NIPAL2 gene. This alteration results from a G to A substitution at nucleotide position 101, causing the glycine (G) at amino acid position 34 to be replaced by an aspartic acid (D). 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

Benign

0.22

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.092

.;T

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.72

T;T

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.40

T;T

MetaSVM

Uncertain

0.21

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

0.69

N;N

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.0

N;N

REVEL

Uncertain

0.44

Sift

Benign

0.071

T;T

Sift4G

Benign

0.30

T;T

Polyphen

1.0

.;D

Vest4

0.32

MutPred

0.34

Loss of catalytic residue at G32 (P = 0.0425);Loss of catalytic residue at G32 (P = 0.0425);

MVP

0.75

MPC

0.70

ClinPred

0.93

GERP RS

3.6

Varity_R

0.17

gMVP

0.43

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over