8-98294038-C-T

Variant summary

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

The NM_001321635.2(NIPAL2):​c.100G>A​(p.Gly34Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000743 in 1,345,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: 7.4e-7 ( 0 hom. )

Consequence

NIPAL2
NM_001321635.2 missense

Scores

2
5
12

Clinical Significance

Not reported in ClinVar

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]

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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=0.3641048).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NIPAL2NM_001321635.2 linkc.100G>A p.Gly34Ser missense_variant Exon 1 of 11 ENST00000430223.7 NP_001308564.1 Q9H841-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NIPAL2ENST00000430223.7 linkc.100G>A p.Gly34Ser missense_variant Exon 1 of 11 1 NM_001321635.2 ENSP00000407087.2 Q9H841-2
NIPAL2ENST00000341166.3 linkc.100G>A p.Gly34Ser missense_variant Exon 1 of 12 2 ENSP00000339256.3 Q9H841-1
NIPAL2ENST00000519324.1 linkn.73G>A non_coding_transcript_exon_variant Exon 1 of 3 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.43e-7
AC:
1
AN:
1345114
Hom.:
0
Cov.:
30
AF XY:
0.00000151
AC XY:
1
AN XY:
662940
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000348
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.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.020
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.089
.;T
Eigen
Benign
0.13
Eigen_PC
Benign
0.14
FATHMM_MKL
Benign
0.68
D
LIST_S2
Benign
0.73
T;T
M_CAP
Pathogenic
0.98
D
MetaRNN
Benign
0.36
T;T
MetaSVM
Uncertain
0.14
D
MutationAssessor
Uncertain
2.1
M;M
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-0.72
N;N
REVEL
Benign
0.28
Sift
Benign
0.046
D;D
Sift4G
Benign
0.37
T;T
Polyphen
1.0
.;D
Vest4
0.26
MutPred
0.31
Gain of glycosylation at G34 (P = 0.0374);Gain of glycosylation at G34 (P = 0.0374);
MVP
0.70
MPC
0.51
ClinPred
0.95
D
GERP RS
4.5
Varity_R
0.22
gMVP
0.39

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.

Other links and lift over

hg19: chr8-99306266; API