Genetic Variant NIPAL3:p.Gly164Ser (chr1-24449576-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020448.5(NIPAL3):c.490G>A(p.Gly164Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000889 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

NIPAL3
NM_020448.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.13

Publications

0 publications found

Variant links:

Genes affected

NIPAL3 (HGNC:25233): (NIPA like domain containing 3) 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]

NIPAL3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020448.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NIPAL3	NM_020448.5	MANE Select	c.490G>A	p.Gly164Ser	missense	Exon 6 of 12	NP_065181.1	Q6P499-1
NIPAL3	NM_001322854.2		c.490G>A	p.Gly164Ser	missense	Exon 6 of 12	NP_001309783.1	Q6P499-1
NIPAL3	NM_001322855.2		c.490G>A	p.Gly164Ser	missense	Exon 7 of 13	NP_001309784.1	Q6P499-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NIPAL3	ENST00000374399.9	TSL:1 MANE Select	c.490G>A	p.Gly164Ser	missense	Exon 6 of 12	ENSP00000363520.4	Q6P499-1
NIPAL3	ENST00000003912.9	TSL:1	c.244G>A	p.Gly82Ser	missense	Exon 7 of 13	ENSP00000003912.3
NIPAL3	ENST00000358028.8	TSL:1	c.490G>A	p.Gly164Ser	missense	Exon 6 of 8	ENSP00000350722.4	Q6P499-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251290

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461806

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53354

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

1111996

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000470

Hom.:

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

0.24

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

Eigen

Uncertain

0.61

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.053

MetaRNN

Uncertain

0.55

MetaSVM

Uncertain

0.46

MutationAssessor

Benign

1.5

PhyloP100

7.1

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.43

REVEL

Uncertain

0.42

Sift

Benign

0.17

Sift4G

Uncertain

0.048

Polyphen

0.92

Vest4

0.57

MutPred

0.50

Gain of disorder (P = 0.0701)

MVP

0.76

MPC

0.68

ClinPred

0.66

GERP RS

6.2

Varity_R

0.28

gMVP

0.57

Mutation Taster

=60/40

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over