X-50088749-C-A

Variant names:

• chrX-50088749-C-A
• rs797044811
• NM_001127898.4:c.1609C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001127898.4(CLCN5):​c.1609C>A​(p.Arg537Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). Synonymous variant affecting the same amino acid position (i.e. R537R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: CLCN5 NM_001127898.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.878
• Publications: 0 publications found

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]

CLCN5 Gene-Disease associations (from GenCC):

• Dent disease type 1

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP7: Synonymous conserved (PhyloP=0.878 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127898.4. 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
	CLCN5	NM_001127898.4	MANE Select	c.1609C>A	p.Arg537Arg	synonymous	Exon 12 of 15	NP_001121370.1	P51795-2
	CLCN5	NM_001440756.1		c.1621C>A	p.Arg541Arg	synonymous	Exon 12 of 15	NP_001427685.1
	CLCN5	NM_001440757.1		c.1621C>A	p.Arg541Arg	synonymous	Exon 12 of 15	NP_001427686.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCN5	ENST00000376091.8	TSL:2 MANE Select	c.1609C>A	p.Arg537Arg	synonymous	Exon 12 of 15	ENSP00000365259.3	P51795-2
	CLCN5	ENST00000307367.2	TSL:1	c.1399C>A	p.Arg467Arg	synonymous	Exon 9 of 12	ENSP00000304257.2	P51795-1
	CLCN5	ENST00000376108.7	TSL:1	c.1399C>A	p.Arg467Arg	synonymous	Exon 9 of 12	ENSP00000365276.3	P51795-1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	14
DANN	Benign	0.69
PhyloP100		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs797044811; hg19: chrX-49853406;