chr1-1281608-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001130413.4(SCNN1D):​c.275C>G​(p.Thr92Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,382,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T92K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 7.2e-7 ( 0 hom. )

Consequence

SCNN1D
NM_001130413.4 missense, splice_region

Scores

2
15
Splicing: ADA: 0.0002073
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.76
Variant links:
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08874938).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SCNN1DNM_001130413.4 linkc.275C>G p.Thr92Arg missense_variant, splice_region_variant Exon 3 of 18 ENST00000379116.10 NP_001123885.2 P51172-3
SCNN1DNR_037668.3 linkn.501C>G splice_region_variant, non_coding_transcript_exon_variant Exon 3 of 17

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SCNN1DENST00000379116.10 linkc.275C>G p.Thr92Arg missense_variant, splice_region_variant Exon 3 of 18 5 NM_001130413.4 ENSP00000368411.5 P51172-3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.23e-7
AC:
1
AN:
1382688
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
682270
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000280
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.080
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
8.8
DANN
Benign
0.57
Eigen
Benign
-0.73
Eigen_PC
Benign
-0.91
FATHMM_MKL
Benign
0.046
N
LIST_S2
Benign
0.25
T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.089
T
MetaSVM
Benign
-0.95
T
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.040
N
REVEL
Benign
0.14
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Vest4
0.075
MutPred
0.33
Gain of methylation at T92 (P = 0.0191);
MVP
0.20
ClinPred
0.13
T
GERP RS
0.93
Varity_R
0.13
gMVP
0.054

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00021
dbscSNV1_RF
Benign
0.080
SpliceAI score (max)
0.15
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-1216988; API