rs137852709
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_000336.3(SCNN1B):c.800C>T(p.Pro267Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,614,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
SCNN1B
NM_000336.3 missense
NM_000336.3 missense
Scores
7
10
2
Clinical Significance
Conservation
PhyloP100: 5.80
Genes affected
SCNN1B (HGNC:10600): (sodium channel epithelial 1 subunit beta) 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 beta subunit, and mutations in this gene have been associated with pseudohypoaldosteronism type 1 (PHA1), and Liddle syndrome. [provided by RefSeq, Apr 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.978
PP5
?
Variant 16-23367879-C-T is Pathogenic according to our data. Variant chr16-23367879-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 8838.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCNN1B | NM_000336.3 | c.800C>T | p.Pro267Leu | missense_variant | 5/13 | ENST00000343070.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCNN1B | ENST00000343070.7 | c.800C>T | p.Pro267Leu | missense_variant | 5/13 | 1 | NM_000336.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152240Hom.: 0 Cov.: 34
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461794Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727204
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152240Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74370
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Bronchiectasis with or without elevated sweat chloride 1;C5774176:Autosomal recessive pseudohypoaldosteronism type 1;CN031472:Liddle syndrome 1 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Dec 03, 2021 | - - |
Bronchiectasis with or without elevated sweat chloride 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 15, 2005 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;.;.;.
MutationTaster
Benign
A;A;A;A
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;.;.;.
Vest4
MutPred
Gain of catalytic residue at P267 (P = 0.1626);.;Gain of catalytic residue at P267 (P = 0.1626);.;
MVP
MPC
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