rs748204541
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_004415.4(DSP):c.363C>T(p.Leu121=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,614,070 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000028 ( 0 hom. )
Consequence
DSP
NM_004415.4 synonymous
NM_004415.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -6.29
Genes affected
DSP (HGNC:3052): (desmoplakin) This gene encodes a protein that anchors intermediate filaments to desmosomal plaques and forms an obligate component of functional desmosomes. Mutations in this gene are the cause of several cardiomyopathies and keratodermas, including skin fragility-woolly hair syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
?
Variant 6-7558205-C-T is Benign according to our data. Variant chr6-7558205-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 413269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-6.3 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.363C>T | p.Leu121= | synonymous_variant | 3/24 | ENST00000379802.8 | |
DSP | NM_001319034.2 | c.363C>T | p.Leu121= | synonymous_variant | 3/24 | ||
DSP | NM_001008844.3 | c.363C>T | p.Leu121= | synonymous_variant | 3/24 | ||
DSP | NM_001406591.1 | c.363C>T | p.Leu121= | synonymous_variant | 3/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.363C>T | p.Leu121= | synonymous_variant | 3/24 | 1 | NM_004415.4 | P2 | |
DSP | ENST00000418664.2 | c.363C>T | p.Leu121= | synonymous_variant | 3/24 | 1 | A2 | ||
DSP | ENST00000710359.1 | c.363C>T | p.Leu121= | synonymous_variant | 3/24 | A2 | |||
DSP | ENST00000683563.1 | n.255C>T | non_coding_transcript_exon_variant | 3/4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152184Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
4
AN:
152184
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251436Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135892
GnomAD3 exomes
AF:
AC:
8
AN:
251436
Hom.:
AF XY:
AC XY:
5
AN XY:
135892
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000280 AC: 41AN: 1461886Hom.: 0 Cov.: 33 AF XY: 0.0000275 AC XY: 20AN XY: 727244
GnomAD4 exome
AF:
AC:
41
AN:
1461886
Hom.:
Cov.:
33
AF XY:
AC XY:
20
AN XY:
727244
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152184Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74344
GnomAD4 genome
?
AF:
AC:
4
AN:
152184
Hom.:
Cov.:
33
AF XY:
AC XY:
2
AN XY:
74344
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 05, 2024 | - - |
Arrhythmogenic right ventricular dysplasia 8;C1854063:Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 11, 2023 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 08, 2018 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 23, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at