NM_020708.5:c.1583G>T

Variant names:

• chr20-46045891-G-T
• NM_020708.5:c.1583G>T

Variant summary

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

The NM_020708.5(SLC12A5):​c.1583G>T​(p.Gly528Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,758 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC12A5 NM_020708.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.08

Genes affected

SLC12A5 (HGNC:13818): (solute carrier family 12 member 5) K-Cl cotransporters are proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The protein encoded by this gene is an integral membrane K-Cl cotransporter that can function in either a net efflux or influx pathway, depending on the chemical concentration gradients of potassium and chloride. The encoded protein can act as a homomultimer, or as a heteromultimer with other K-Cl cotransporters, to maintain chloride homeostasis in neurons. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Sep 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
SLC12A5	NM_020708.5	c.1583G>T	p.Gly528Val	missense_variant	Exon 13 of 26	ENST00000243964.7	NP_065759.1
SLC12A5	NM_001134771.2	c.1652G>T	p.Gly551Val	missense_variant	Exon 13 of 26		NP_001128243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A5	ENST00000243964.7	c.1583G>T	p.Gly528Val	missense_variant	Exon 13 of 26	1	NM_020708.5	ENSP00000243964.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461758 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727190

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Pathogenic	0.86	D;.
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Uncertain	0.68	D
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.5	D;D
REVEL	Pathogenic	0.78
Sift	Benign	0.37	T;T
Sift4G	Benign	0.50	T;T
Polyphen		0.55	P;B
Vest4		0.69
MutPred		0.57		Loss of disorder (P = 0.0334);.;
MVP		0.87
MPC		2.3
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.87
gMVP		0.92

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-44674530;