8-98294038-C-T

Variant names:

• chr8-98294038-C-T
• NM_001321635.2:c.100G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15

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]

LOC105375659 (HGNC:):

ACMG classification

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
NIPAL2	NM_001321635.2	c.100G>A	p.Gly34Ser	missense_variant	Exon 1 of 11	ENST00000430223.7	NP_001308564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIPAL2	ENST00000430223.7	c.100G>A	p.Gly34Ser	missense_variant	Exon 1 of 11	1	NM_001321635.2	ENSP00000407087.2
NIPAL2	ENST00000341166.3	c.100G>A	p.Gly34Ser	missense_variant	Exon 1 of 12	2		ENSP00000339256.3
NIPAL2	ENST00000519324.1	n.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

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;