NM_001127898.4:c.292C>G

Variant names:

• chrX-50070007-C-G
• rs1049618423
• NM_001127898.4:c.292C>G

Variant summary

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

The NM_001127898.4(CLCN5):​c.292C>G​(p.Arg98Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: CLCN5 NM_001127898.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94

Genes affected

CLCN5 (HGNC:2023): (chloride voltage-gated channel 5) This gene encodes a member of the ClC family of chloride ion channels and ion transporters. The encoded protein is primarily localized to endosomal membranes and may function to facilitate albumin uptake by the renal proximal tubule. Mutations in this gene have been found in Dent disease and renal tubular disorders complicated by nephrolithiasis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLCN5	NM_001127898.4	c.292C>G	p.Arg98Gly	missense_variant	Exon 5 of 15	ENST00000376091.8	NP_001121370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCN5	ENST00000376091.8	c.292C>G	p.Arg98Gly	missense_variant	Exon 5 of 15	2	NM_001127898.4	ENSP00000365259.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.86	.;.;D;D;D
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.97	.;D;.;.;D
M_CAP	Pathogenic	0.40	D
MetaRNN	Uncertain	0.59	D;D;D;D;D
MetaSVM	Uncertain	0.58	D
MutationAssessor	Uncertain	2.5	.;.;M;M;M
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-6.0	D;D;D;.;D
REVEL	Pathogenic	0.73
Sift	Uncertain	0.0020	D;D;D;.;D
Sift4G	Uncertain	0.0050	D;D;D;.;D
Polyphen		0.76	P;P;P;P;P
Vest4		0.46
MutPred		0.47		.;.;Loss of MoRF binding (P = 0.0183);Loss of MoRF binding (P = 0.0183);Loss of MoRF binding (P = 0.0183);
MVP		0.88
MPC		0.84
ClinPred		0.99	D
GERP RS		3.5
Varity_R		0.86
gMVP		0.89

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: rs1049618423; hg19: chrX-49834662;