8-98294025-C-G

Variant names:

• chr8-98294025-C-G
• rs751345147
• NM_001321635.2:c.113G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001321635.2(NIPAL2):​c.113G>C​(p.Gly38Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000201 in 1,496,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. G38D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: NIPAL2 NM_001321635.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15891287).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPAL2	NM_001321635.2	c.113G>C	p.Gly38Ala	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.113G>C	p.Gly38Ala	missense_variant	Exon 1 of 11	1	NM_001321635.2	ENSP00000407087.2
NIPAL2	ENST00000341166.3	c.113G>C	p.Gly38Ala	missense_variant	Exon 1 of 12	2		ENSP00000339256.3
NIPAL2	ENST00000519324.1	n.86G>C		non_coding_transcript_exon_variant	Exon 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152128 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000149 AC: 2 AN: 1344128 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 662436

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: 0.00000190

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152128 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74304

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.098	.;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.62	T;T
M_CAP	Pathogenic	0.98	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	2.0	M;M
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.61	N;N
REVEL	Benign	0.15
Sift	Benign	0.10	T;T
Sift4G	Benign	0.33	T;T
Polyphen		0.36	.;B
Vest4		0.12
MutPred		0.41		Loss of glycosylation at S37 (P = 0.0539);Loss of glycosylation at S37 (P = 0.0539);
MVP		0.64
MPC		0.16
ClinPred		0.15	T
GERP RS		2.0
Varity_R		0.096
gMVP		0.23

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

LitVar

Other links and lift over

dbSNP: rs751345147; hg19: chr8-99306253;