rs751345147

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr8-98294025-C-A
• chr8-98294025-C-G
• chr8-98294025-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001321635.2(NIPAL2):​c.113G>T​(p.Gly38Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000149 in 1,344,128 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. G38D) has been classified as Uncertain significance.

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

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22987634).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIPAL2	NM_001321635.2	MANE Select	c.113G>T	p.Gly38Val	missense	Exon 1 of 11	NP_001308564.1	Q9H841-2
	NIPAL2	NM_024759.3		c.113G>T	p.Gly38Val	missense	Exon 1 of 12	NP_079035.1	Q9H841-1
	NIPAL2	NM_001321636.2		c.113G>T	p.Gly38Val	missense	Exon 1 of 10	NP_001308565.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIPAL2	ENST00000430223.7	TSL:1 MANE Select	c.113G>T	p.Gly38Val	missense	Exon 1 of 11	ENSP00000407087.2	Q9H841-2
	NIPAL2	ENST00000852806.1		c.113G>T	p.Gly38Val	missense	Exon 1 of 11	ENSP00000522865.1
	NIPAL2	ENST00000341166.3	TSL:2	c.113G>T	p.Gly38Val	missense	Exon 1 of 12	ENSP00000339256.3	Q9H841-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000149 AC: 2 AN: 1344128 Hom.: 0 Cov.: 31 AF XY: 0.00000151 AC XY: 1 AN XY: 662436

African (AFR) AF: 0.0000738 AC: 2 AN: 27092

American (AMR) AF: 0.00 AC: 0 AN: 28554

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23648

East Asian (EAS) AF: 0.00 AC: 0 AN: 28752

South Asian (SAS) AF: 0.00 AC: 0 AN: 74058

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4874

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1054710

Other (OTH) AF: 0.00 AC: 0 AN: 55452

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.70	T
M_CAP	Pathogenic	0.99	D
MetaRNN	Benign	0.23	T
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.5
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.24
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.057	T
Polyphen		0.91	P
Vest4		0.18
MutPred		0.49		Loss of disorder (P = 0.0173)
MVP		0.75
MPC		0.24
ClinPred		0.77	D
GERP RS		2.0
PromoterAI		0.040	Neutral
Varity_R		0.22
gMVP		0.32
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs751345147; hg19: chr8-99306253;