1-16029233-T-A

Variant names:

• chr1-16029233-T-A
• NM_004070.4:c.1161T>A
• CLCNKA p.Leu387Leu

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_004070.4(CLCNKA):​c.1161T>A​(p.Leu387Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L387L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CLCNKA NM_004070.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380
• Publications: 0 publications found

Genes affected

CLCNKA (HGNC:2026): (chloride voltage-gated channel Ka) This gene is a member of the CLC family of voltage-gated chloride channels. The encoded protein is predicted to have 12 transmembrane domains, and requires a beta subunit called barttin to form a functional channel. It is thought to function in salt reabsorption in the kidney and potassium recycling in the inner ear. The gene is highly similar to CLCNKB, which is located 10 kb downstream from this gene. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CLCNKA Gene-Disease associations (from GenCC):

• Bartter disease type 4B

  Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, G2P
• Bartter syndrome type 4

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=0.038 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004070.4. 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
	CLCNKA	NM_004070.4	MANE Select	c.1161T>A	p.Leu387Leu	synonymous	Exon 12 of 20	NP_004061.3
	CLCNKA	NM_001042704.2		c.1161T>A	p.Leu387Leu	synonymous	Exon 12 of 20	NP_001036169.1	P51800-3
	CLCNKA	NM_001257139.2		c.1032T>A	p.Leu344Leu	synonymous	Exon 11 of 19	NP_001244068.1	P51800-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLCNKA	ENST00000331433.5	TSL:1 MANE Select	c.1161T>A	p.Leu387Leu	synonymous	Exon 12 of 20	ENSP00000332771.4	P51800-1
	CLCNKA	ENST00000375692.5	TSL:1	c.1161T>A	p.Leu387Leu	synonymous	Exon 13 of 21	ENSP00000364844.1	P51800-3
	CLCNKA	ENST00000861487.1		c.1161T>A	p.Leu387Leu	synonymous	Exon 12 of 20	ENSP00000531546.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.8
DANN	Benign	0.53
PhyloP100		0.038
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-16355728;