Variant 8-98212477-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001321635.2(NIPAL2):c.583A>G(p.Ile195Val) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

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: 0.427

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:

NIPAL2-AS1 (HGNC:):

NIPAL2-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13126907).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIPAL2	NM_001321635.2 linkuse as main transcript	c.583A>G	p.Ile195Val	missense_variant	6/11	ENST00000430223.7	NP_001308564.1
NIPAL2-AS1	XR_928444.3 linkuse as main transcript	n.662+32433T>C		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.583A>G	p.Ile195Val	missense_variant	6/11	1	NM_001321635.2	ENSP00000407087	P1	Q9H841-2
NIPAL2	ENST00000341166.3 linkuse as main transcript	c.583A>G	p.Ile195Val	missense_variant	6/12	2		ENSP00000339256		Q9H841-1
NIPAL2	ENST00000520545.5 linkuse as main transcript	n.602A>G		non_coding_transcript_exon_variant	5/10	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1355950

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

680718

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

Jan 30, 2024

The c.583A>G (p.I195V) alteration is located in exon 6 (coding exon 6) of the NIPAL2 gene. This alteration results from a A to G substitution at nucleotide position 583, causing the isoleucine (I) at amino acid position 195 to be replaced by a valine (V). 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

0.073

BayesDel_addAF

Benign

-0.034

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.28

.;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.0082

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.72

N;N

MutationTaster

Benign

0.91

D;D

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.14

N;N

REVEL

Benign

0.23

Sift

Benign

0.59

T;T

Sift4G

Benign

0.61

T;T

Polyphen

0.0010

.;B

Vest4

0.075

MutPred

0.62

Gain of catalytic residue at I195 (P = 0.0638);Gain of catalytic residue at I195 (P = 0.0638);

MVP

0.49

MPC

0.13

ClinPred

0.096

GERP RS

0.59

Varity_R

0.037

gMVP

0.20

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