1-1286079-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001130413.4(SCNN1D):c.712C>T(p.Arg238Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000405 in 1,605,158 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000041 ( 0 hom. )
Consequence
SCNN1D
NM_001130413.4 missense
NM_001130413.4 missense
Scores
2
7
8
Clinical Significance
Conservation
PhyloP100: 1.59
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCNN1D | NM_001130413.4 | c.712C>T | p.Arg238Cys | missense_variant | 7/18 | ENST00000379116.10 | |
SCNN1D | NR_037668.3 | n.844C>T | non_coding_transcript_exon_variant | 6/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCNN1D | ENST00000379116.10 | c.712C>T | p.Arg238Cys | missense_variant | 7/18 | 5 | NM_001130413.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152246Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000394 AC: 9AN: 228524Hom.: 0 AF XY: 0.0000560 AC XY: 7AN XY: 124944
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GnomAD4 exome AF: 0.0000413 AC: 60AN: 1452912Hom.: 0 Cov.: 32 AF XY: 0.0000429 AC XY: 31AN XY: 722174
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152246Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3AN XY: 74378
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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 | Nov 30, 2022 | The c.712C>T (p.R238C) 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 712, causing the arginine (R) at amino acid position 238 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;.;T;D;T
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D
Vest4
MVP
ClinPred
T
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