18-31318331-A-G
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001942.4(DSG1):c.31A>G(p.Met11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 1,610,274 control chromosomes in the GnomAD database, including 178,730 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.45 ( 15946 hom., cov: 32)
Exomes 𝑓: 0.46 ( 162784 hom. )
Consequence
DSG1
NM_001942.4 missense
NM_001942.4 missense
Scores
18
Clinical Significance
Conservation
PhyloP100: 1.46
Genes affected
DSG1 (HGNC:3048): (desmoglein 1) This gene encodes a member of the desmoglein protein subfamily. Desmogleins, along with desmocollins, are cadherin-like transmembrane glycoproteins that are major components of the desmosome. Desmosomes are cell-cell junctions that help resist shearing forces and are found in high concentrations in cells subject to mechanical stress. This gene is found in a cluster with other desmoglein family members on chromosome 18. The encoded protein has been identified as a target of auto-antibodies in the autoimmune skin blistering disease pemphigus foliaceus. Disruption of this gene has also been associated with the skin diseases palmoplantar keratoderma and erythroderma. [provided by RefSeq, Feb 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=2.0042062E-4).
BP6
?
Variant 18-31318331-A-G is Benign according to our data. Variant chr18-31318331-A-G is described in ClinVar as [Benign]. Clinvar id is 402801.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSG1 | NM_001942.4 | c.31A>G | p.Met11Val | missense_variant | 1/15 | ENST00000257192.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSG1 | ENST00000257192.5 | c.31A>G | p.Met11Val | missense_variant | 1/15 | 1 | NM_001942.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.446 AC: 67773AN: 151900Hom.: 15949 Cov.: 32
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GnomAD3 exomes AF: 0.422 AC: 105843AN: 250724Hom.: 25070 AF XY: 0.435 AC XY: 59016AN XY: 135598
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GnomAD4 exome AF: 0.464 AC: 676571AN: 1458256Hom.: 162784 Cov.: 35 AF XY: 0.466 AC XY: 337985AN XY: 725604
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GnomAD4 genome ? AF: 0.446 AC: 67795AN: 152018Hom.: 15946 Cov.: 32 AF XY: 0.447 AC XY: 33241AN XY: 74310
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 27, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Palmoplantar keratoderma i, striate, focal, or diffuse Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
Severe dermatitis-multiple allergies-metabolic wasting syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
P
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MPC
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