rs121909138

Variant names:

• chr1-16027432-C-G
• rs121909138
• NM_004070.4:c.778C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-16027432-C-G
• chr1-16027432-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004070.4(CLCNKA):​c.778C>G​(p.Gln260Glu) variant causes a missense 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. 16/22 in silico tools predict 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: 33)
• Consequence: CLCNKA NM_004070.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• Publications: 4 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.069546044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLCNKA	NM_004070.4	c.778C>G	p.Gln260Glu	missense_variant	Exon 8 of 20	ENST00000331433.5	NP_004061.3
CLCNKA	NM_001042704.2	c.778C>G	p.Gln260Glu	missense_variant	Exon 8 of 20		NP_001036169.1
CLCNKA	NM_001257139.2	c.649C>G	p.Gln217Glu	missense_variant	Exon 7 of 19		NP_001244068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLCNKA	ENST00000331433.5	c.778C>G	p.Gln260Glu	missense_variant	Exon 8 of 20	1	NM_004070.4	ENSP00000332771.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	12
DANN	Benign	0.76
DEOGEN2	Benign	0.27	.;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.80	T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.070	T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.52	N;.;N
PhyloP100		0.12
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.38	N;N;N
REVEL	Benign	0.20
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0030	.;.;B
Vest4		0.37
MutPred		0.38		Gain of disorder (P = 0.0423);.;Gain of disorder (P = 0.0423);
MVP		0.46
MPC		0.39
ClinPred		0.036	T
GERP RS		-0.42
Varity_R		0.085
gMVP		0.18
Mutation Taster		=88/12	polymorphism

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: rs121909138; hg19: chr1-16353927;