rs754692013

Variant names:

• chr8-98294038-C-A
• rs754692013
• NM_001321635.2:c.100G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-98294038-C-A
• chr8-98294038-C-T

Variant summary

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

The NM_001321635.2(NIPAL2):​c.100G>T​(p.Gly34Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,497,232 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G34D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: NIPAL2 NM_001321635.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.15
• 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.

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.100G>T	p.Gly34Cys	missense	Exon 1 of 11	NP_001308564.1	Q9H841-2
	NIPAL2	NM_024759.3		c.100G>T	p.Gly34Cys	missense	Exon 1 of 12	NP_079035.1	Q9H841-1
	NIPAL2	NM_001321636.2		c.100G>T	p.Gly34Cys	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.100G>T	p.Gly34Cys	missense	Exon 1 of 11	ENSP00000407087.2	Q9H841-2
	NIPAL2	ENST00000852806.1		c.100G>T	p.Gly34Cys	missense	Exon 1 of 11	ENSP00000522865.1
	NIPAL2	ENST00000341166.3	TSL:2	c.100G>T	p.Gly34Cys	missense	Exon 1 of 12	ENSP00000339256.3	Q9H841-1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152118 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000265

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 99236 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000112 AC: 15 AN: 1345114 Hom.: 0 Cov.: 30 AF XY: 0.00000905 AC XY: 6 AN XY: 662940

African (AFR) AF: 0.000516 AC: 14 AN: 27116

American (AMR) AF: 0.00 AC: 0 AN: 28590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23704

East Asian (EAS) AF: 0.00 AC: 0 AN: 28738

South Asian (SAS) AF: 0.00 AC: 0 AN: 74186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4882

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1055292

Other (OTH) AF: 0.0000180 AC: 1 AN: 55482

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152118 Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8 AN XY: 74308

African (AFR) AF: 0.000265 AC: 11 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000117

ExAC AF: 0.0000251 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.71	T
M_CAP	Pathogenic	0.97	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Uncertain	0.73	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.1
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.59
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.016	D
Polyphen		1.0	D
Vest4		0.41
MVP		0.78
MPC		0.65
ClinPred		0.97	D
GERP RS		4.5
PromoterAI		-0.036	Neutral
Varity_R		0.38
gMVP		0.52
Mutation Taster		=87/13	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: rs754692013; hg19: chr8-99306266;