15-34236719-G-C

Variant names:

• chr15-34236719-G-C
• NM_001365088.1:c.3031C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001365088.1(SLC12A6):​c.3031C>G​(p.Arg1011Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC12A6 NM_001365088.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.450

Genes affected

SLC12A6 (HGNC:10914): (solute carrier family 12 member 6) This gene is a member of the K-Cl cotransporter (KCC) family. K-Cl cotransporters are integral membrane proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The proteins encoded by this gene are activated by cell swelling induced by hypotonic conditions. Alternate splicing results in multiple transcript variants encoding different isoforms. Mutations in this gene are associated with agenesis of the corpus callosum with peripheral neuropathy. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A6	NM_001365088.1	c.3031C>G	p.Arg1011Gly	missense_variant	Exon 23 of 26	ENST00000354181.8	NP_001352017.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A6	ENST00000354181.8	c.3031C>G	p.Arg1011Gly	missense_variant	Exon 23 of 26	1	NM_001365088.1	ENSP00000346112.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.75	.;.;D;D;.;.;D;D;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.83	T;T;.;.;.;T;T;T;T
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.65	D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.35	D
MutationAssessor	Uncertain	2.5	.;.;M;M;.;.;.;M;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.2	D;D;D;D;D;D;D;D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.017	D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.056	T;T;T;T;T;T;T;T;T
Polyphen		0.34, 0.89, 0.78	.;B;P;P;.;.;P;P;.
Vest4		0.75
MutPred		0.32		.;.;Gain of relative solvent accessibility (P = 0.0275);Gain of relative solvent accessibility (P = 0.0275);.;.;.;Gain of relative solvent accessibility (P = 0.0275);.;
MVP		0.71
MPC		2.4
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.50
gMVP		0.89

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-34528920;