rs193920773
Positions:
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_001038.6(SCNN1A):āc.1129A>Gā(p.Ile377Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,613,230 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 Uncertain significance (no stars).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 0.0000027 ( 0 hom. )
Consequence
SCNN1A
NM_001038.6 missense
NM_001038.6 missense
Scores
7
10
Clinical Significance
Conservation
PhyloP100: 4.19
Genes affected
SCNN1A (HGNC:10599): (sodium channel epithelial 1 subunit alpha) 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 alpha subunit, and mutations in this gene have been associated with pseudohypoaldosteronism type 1 (PHA1), a rare salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Apr 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.41792065).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCNN1A | NM_001038.6 | c.1129A>G | p.Ile377Val | missense_variant | 6/13 | ENST00000228916.7 | |
LOC107984500 | XR_007063191.1 | n.297-239T>C | intron_variant, non_coding_transcript_variant | ||||
SCNN1A | NM_001159576.2 | c.1306A>G | p.Ile436Val | missense_variant | 5/12 | ||
SCNN1A | NM_001159575.2 | c.1198A>G | p.Ile400Val | missense_variant | 6/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCNN1A | ENST00000228916.7 | c.1129A>G | p.Ile377Val | missense_variant | 6/13 | 1 | NM_001038.6 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152158Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000803 AC: 2AN: 248920Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134676
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460954Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 726658
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152276Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74460
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Malignant tumor of prostate Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | Science for Life laboratory, Karolinska Institutet | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Uncertain
Sift
Benign
D;D;D;D;D
Sift4G
Uncertain
D;D;D;T;D
Polyphen
B;.;P;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
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gMVP
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