chr16-56865277-T-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001126108.2(SLC12A3):​c.42T>G​(p.Thr14=) 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Consequence

SLC12A3
NM_001126108.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.112
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
Variant 16-56865277-T-G is Benign according to our data. Variant chr16-56865277-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1103773.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.112 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC12A3NM_001126108.2 linkuse as main transcriptc.42T>G p.Thr14= synonymous_variant 1/26 ENST00000563236.6
SLC12A3NM_000339.3 linkuse as main transcriptc.42T>G p.Thr14= synonymous_variant 1/26
SLC12A3NM_001126107.2 linkuse as main transcriptc.42T>G p.Thr14= synonymous_variant 1/26
SLC12A3NM_001410896.1 linkuse as main transcriptc.42T>G p.Thr14= synonymous_variant 1/26

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC12A3ENST00000563236.6 linkuse as main transcriptc.42T>G p.Thr14= synonymous_variant 1/261 NM_001126108.2 A1P55017-1
SLC12A3ENST00000438926.6 linkuse as main transcriptc.42T>G p.Thr14= synonymous_variant 1/261 A1P55017-2
SLC12A3ENST00000566786.5 linkuse as main transcriptc.42T>G p.Thr14= synonymous_variant 1/261 P4P55017-3
SLC12A3ENST00000262502.5 linkuse as main transcriptc.42T>G p.Thr14= synonymous_variant 1/265 A1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeSep 14, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
CADD
Benign
1.9
DANN
Benign
0.64

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: chr16-56899189; API