rs781300869
Positions:
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_000338.3(SLC12A1):c.993G>A(p.Leu331=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 1,456,504 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
SLC12A1
NM_000338.3 synonymous
NM_000338.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.373
Genes affected
SLC12A1 (HGNC:10910): (solute carrier family 12 member 1) This gene encodes a kidney-specific sodium-potassium-chloride cotransporter that is expressed on the luminal membrane of renal epithelial cells of the thick ascending limb of Henle's loop and the macula densa. It plays a key role in concentrating urine and accounts for most of the NaCl resorption. It is sensitive to such diuretics as furosemide and bumetanide. Some Bartter-like syndromes result from defects in this gene. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional splice variants have been described but their biological validity in humans has not been experimentally proven.[provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
Variant 15-48232744-G-A is Benign according to our data. Variant chr15-48232744-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 255875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.373 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC12A1 | NM_000338.3 | c.993G>A | p.Leu331= | synonymous_variant | 8/27 | ENST00000380993.8 | |
SLC12A1 | NM_001184832.2 | c.993G>A | p.Leu331= | synonymous_variant | 8/27 | ||
SLC12A1 | NM_001384136.1 | c.993G>A | p.Leu331= | synonymous_variant | 8/27 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC12A1 | ENST00000380993.8 | c.993G>A | p.Leu331= | synonymous_variant | 8/27 | 5 | NM_000338.3 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 250970Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135638
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GnomAD4 exome AF: 0.00000549 AC: 8AN: 1456504Hom.: 0 Cov.: 29 AF XY: 0.00000552 AC XY: 4AN XY: 725008
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GnomAD4 genome ? Cov.: 33
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33
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Apr 06, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at