Genetic Variant NIPAL2:p.Gly34Asp (chr8-98294037-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G34C) has been classified 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

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321635.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NIPAL2	NM_001321635.2	MANE Select	c.101G>A	p.Gly34Asp	missense	Exon 1 of 11	NP_001308564.1	Q9H841-2
NIPAL2	NM_024759.3		c.101G>A	p.Gly34Asp	missense	Exon 1 of 12	NP_079035.1	Q9H841-1
NIPAL2	NM_001321636.2		c.101G>A	p.Gly34Asp	missense	Exon 1 of 10	NP_001308565.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NIPAL2	ENST00000430223.7	TSL:1 MANE Select	c.101G>A	p.Gly34Asp	missense	Exon 1 of 11	ENSP00000407087.2	Q9H841-2
NIPAL2	ENST00000852806.1		c.101G>A	p.Gly34Asp	missense	Exon 1 of 11	ENSP00000522865.1
NIPAL2	ENST00000341166.3	TSL:2	c.101G>A	p.Gly34Asp	missense	Exon 1 of 12	ENSP00000339256.3	Q9H841-1

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

African (AFR)

AF:

0.00

AC:

AN:

27100

American (AMR)

AF:

0.00

AC:

AN:

28638

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23680

East Asian (EAS)

AF:

0.00

AC:

AN:

28748

South Asian (SAS)

AF:

0.00

AC:

AN:

74170

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47074

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4856

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1055240

Other (OTH)

AF:

0.00

AC:

AN:

55466

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.092

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.72

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.40

MetaSVM

Uncertain

0.21

MutationAssessor

Uncertain

2.1

PhyloP100

3.5

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.0

REVEL

Uncertain

0.44

Sift

Benign

0.071

Sift4G

Benign

0.30

Polyphen

1.0

Vest4

0.32

MutPred

0.34

Loss of catalytic residue at G32 (P = 0.0425)

MVP

0.75

MPC

0.70

ClinPred

0.93

GERP RS

3.6

PromoterAI

0.095

Neutral

(source)

Varity_R

0.17

gMVP

0.43

Mutation Taster

=69/31

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over