rs5734
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001039.4(SCNN1G):āc.387T>Cā(p.Tyr129=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,613,870 control chromosomes in the GnomAD database, including 76,394 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.27 ( 6188 hom., cov: 32)
Exomes š: 0.31 ( 70206 hom. )
Consequence
SCNN1G
NM_001039.4 synonymous
NM_001039.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.39
Genes affected
SCNN1G (HGNC:10602): (sodium channel epithelial 1 subunit gamma) Nonvoltage-gated, amiloride-sensitive, sodium channels control fluid and electrolyte transport across epithelia in many organs. These channels are heteromeric complexes consisting of 3 subunits: alpha, beta, and gamma. This gene encodes the gamma subunit, and mutations in this gene have been associated with Liddle syndrome. [provided by RefSeq, Apr 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
Variant 16-23189440-T-C is Benign according to our data. Variant chr16-23189440-T-C is described in ClinVar as [Benign]. Clinvar id is 165172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23189440-T-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-1.39 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCNN1G | NM_001039.4 | c.387T>C | p.Tyr129= | synonymous_variant | 3/13 | ENST00000300061.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCNN1G | ENST00000300061.3 | c.387T>C | p.Tyr129= | synonymous_variant | 3/13 | 1 | NM_001039.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.272 AC: 41404AN: 152000Hom.: 6165 Cov.: 32
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GnomAD3 exomes AF: 0.309 AC: 77645AN: 251300Hom.: 12885 AF XY: 0.305 AC XY: 41377AN XY: 135852
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GnomAD4 exome AF: 0.306 AC: 447170AN: 1461752Hom.: 70206 Cov.: 42 AF XY: 0.305 AC XY: 221919AN XY: 727182
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GnomAD4 genome ? AF: 0.273 AC: 41478AN: 152118Hom.: 6188 Cov.: 32 AF XY: 0.274 AC XY: 20398AN XY: 74346
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 24, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | Tyr129Tyr in exon 3 of SCNN1G: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 32.1% (2759/8600) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs5734). - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Liddle syndrome 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Autosomal recessive pseudohypoaldosteronism type 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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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