Variant chrX-50042407-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001127898.4(CLCN5):c.108C>T(p.Thr36=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,149,919 control chromosomes in the GnomAD database, including 1,027 homozygotes. There are 3,360 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.061 ( 537 hom., 1819 hem., cov: 23)

Exomes 𝑓: 0.0062 ( 490 hom. 1541 hem. )

Consequence

CLCN5
NM_001127898.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.294

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant X-50042407-C-T is Benign according to our data. Variant chrX-50042407-C-T is described in ClinVar as [Benign]. Clinvar id is 1269710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.294 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLCN5	NM_001127898.4 linkuse as main transcript	c.108C>T	p.Thr36=	synonymous_variant	4/15	ENST00000376091.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCN5	ENST00000376091.8 linkuse as main transcript	c.108C>T	p.Thr36=	synonymous_variant	4/15	2	NM_001127898.4	P3	P51795-2
CLCN5	ENST00000376088.7 linkuse as main transcript	c.108C>T	p.Thr36=	synonymous_variant	4/15	2		P3	P51795-2
CLCN5	ENST00000482218.2 linkuse as main transcript	c.108C>T	p.Thr36=	synonymous_variant	3/3	3
CLCN5	ENST00000643129.1 linkuse as main transcript	c.72C>T	p.Thr24=	synonymous_variant, NMD_transcript_variant	1/14

Frequencies

GnomAD3 genomes

AF:

0.0606

AC:

6746

AN:

111332

Hom.:

537

Cov.:

AF XY:

0.0542

AC XY:

1821

AN XY:

33606

show subpopulations

Gnomad AFR

AF:

0.212

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0199

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00113

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00424

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.0332

GnomAD3 exomes

AF:

0.0137

AC:

1561

AN:

114260

Hom.:

146

AF XY:

0.00481

AC XY:

161

AN XY:

33446

show subpopulations

Gnomad AFR exome

AF:

0.198

Gnomad AMR exome

AF:

0.00694

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000379

Gnomad FIN exome

AF:

0.0000819

Gnomad NFE exome

AF:

0.000283

Gnomad OTH exome

AF:

0.00548

GnomAD4 exome

AF:

0.00618

AC:

6416

AN:

1038534

Hom.:

490

Cov.:

AF XY:

0.00471

AC XY:

1541

AN XY:

327154

show subpopulations

Gnomad4 AFR exome

AF:

0.214

Gnomad4 AMR exome

AF:

0.00994

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000412

Gnomad4 FIN exome

AF:

0.0000265

Gnomad4 NFE exome

AF:

0.000198

Gnomad4 OTH exome

AF:

0.0136

GnomAD4 genome

AF:

0.0605

AC:

6743

AN:

111385

Hom.:

537

Cov.:

AF XY:

0.0540

AC XY:

1819

AN XY:

33669

show subpopulations

Gnomad4 AFR

AF:

0.212

Gnomad4 AMR

AF:

0.0200

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000756

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.0327

Alfa

AF:

0.0315

Hom.:

182

Bravo

AF:

0.0686

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

2.9

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over