1-1286028-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001130413.4(SCNN1D):c.661C>T(p.Arg221Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,569,576 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 (★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
SCNN1D
NM_001130413.4 missense
NM_001130413.4 missense
Scores
3
5
10
Clinical Significance
Conservation
PhyloP100: -1.16
Genes affected
SCNN1D (HGNC:10601): (sodium channel epithelial 1 subunit delta) Predicted to enable ligand-gated sodium channel activity. Predicted to be involved in sodium ion transmembrane transport. Located in actin cytoskeleton and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27090943).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCNN1D | NM_001130413.4 | c.661C>T | p.Arg221Trp | missense_variant | 7/18 | ENST00000379116.10 | |
SCNN1D | NR_037668.3 | n.793C>T | non_coding_transcript_exon_variant | 6/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCNN1D | ENST00000379116.10 | c.661C>T | p.Arg221Trp | missense_variant | 7/18 | 5 | NM_001130413.4 | A2 |
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 152180Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000344 AC: 6AN: 174526Hom.: 0 AF XY: 0.0000212 AC XY: 2AN XY: 94538
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GnomAD4 exome AF: 0.000140 AC: 198AN: 1417278Hom.: 0 Cov.: 32 AF XY: 0.000143 AC XY: 100AN XY: 701222
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GnomAD4 genome AF: 0.000138 AC: 21AN: 152298Hom.: 0 Cov.: 34 AF XY: 0.000134 AC XY: 10AN XY: 74462
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 13, 2023 | The c.661C>T (p.R221W) alteration is located in exon 7 (coding exon 7) of the SCNN1D gene. This alteration results from a C to T substitution at nucleotide position 661, causing the arginine (R) at amino acid position 221 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;.;T;T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
.;N;N;.;.
MutationTaster
Benign
N;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D
Vest4
MVP
ClinPred
D
GERP RS
Varity_R
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