rs8063291

Positions:

• chr16-56896339-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001126108.2(SLC12A3):​c.2633+1697T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,216 control chromosomes in the GnomAD database, including 3,473 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3473 hom., cov: 33)
• Consequence: SLC12A3 NM_001126108.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52

Genes affected

SLC12A3 (HGNC:10912): (solute carrier family 12 member 3) This gene encodes a renal thiazide-sensitive sodium-chloride cotransporter that is important for electrolyte homeostasis. This cotransporter mediates sodium and chloride reabsorption in the distal convoluted tubule. Mutations in this gene cause Gitelman syndrome, a disease similar to Bartter's syndrome, that is characterized by hypokalemic alkalosis combined with hypomagnesemia, low urinary calcium, and increased renin activity associated with normal blood pressure. This cotransporter is the target for thiazide diuretics that are used for treating high blood pressure. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A3	NM_001126108.2	c.2633+1697T>C		intron_variant		ENST00000563236.6	NP_001119580.2
SLC12A3	NM_000339.3	c.2660+1697T>C		intron_variant			NP_000330.3
SLC12A3	NM_001126107.2	c.2657+1697T>C		intron_variant			NP_001119579.2
SLC12A3	NM_001410896.1	c.2630+1697T>C		intron_variant			NP_001397825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A3	ENST00000563236.6	c.2633+1697T>C		intron_variant		1	NM_001126108.2	ENSP00000456149	A1
SLC12A3	ENST00000438926.6	c.2660+1697T>C		intron_variant		1		ENSP00000402152	A1
SLC12A3	ENST00000566786.5	c.2657+1697T>C		intron_variant		1		ENSP00000457552	P4
SLC12A3	ENST00000262502.5	c.2630+1697T>C		intron_variant		5		ENSP00000262502	A1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31983 AN: 152098 Hom.: 3470 Cov.: 33

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.196

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.210 AC: 32014 AN: 152216 Hom.: 3473 Cov.: 33 AF XY: 0.211 AC XY: 15697 AN XY: 74436

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.198

Alfa AF: 0.198 Hom.: 524

Bravo AF: 0.211

Asia WGS AF: 0.279 AC: 970 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.52
DANN	Benign	0.25

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

LitVar

Other links and lift over

dbSNP: rs8063291; hg19: chr16-56930251;