ENST00000307367.2:c.-165C>T

Variant names:

• chrX-50069627-C-T
• rs112064121
• ENST00000307367.2:c.-165C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000307367.2(CLCN5):​c.-165C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000127 in 787,524 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000013 (0 hom. 0 hem.)
• Consequence: CLCN5 ENST00000307367.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000307367.2. 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
	CLCN5	NM_001127898.4	MANE Select	c.164-252C>T		intron	N/A	NP_001121370.1	P51795-2
	CLCN5	NM_001282163.2		c.-105C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	NP_001269092.1
	CLCN5	NM_001282163.2		c.-105C>T		5_prime_UTR	Exon 1 of 12	NP_001269092.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCN5	ENST00000307367.2	TSL:1	c.-165C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	ENSP00000304257.2	P51795-1
	CLCN5	ENST00000307367.2	TSL:1	c.-165C>T		5_prime_UTR	Exon 1 of 12	ENSP00000304257.2	P51795-1
	CLCN5	ENST00000376091.8	TSL:2 MANE Select	c.164-252C>T		intron	N/A	ENSP00000365259.3	P51795-2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000127 AC: 1 AN: 787524 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 223054

African (AFR) AF: 0.00 AC: 0 AN: 17336

American (AMR) AF: 0.00 AC: 0 AN: 6597

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9087

East Asian (EAS) AF: 0.00 AC: 0 AN: 15511

South Asian (SAS) AF: 0.00 AC: 0 AN: 16523

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9971

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1755

European-Non Finnish (NFE) AF: 0.00000147 AC: 1 AN: 679498

Other (OTH) AF: 0.00 AC: 0 AN: 31246

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.38
PhyloP100		0.31
PromoterAI		-0.0049	Neutral

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: rs112064121; hg19: chrX-49834282;