rs200806163
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_004415.4(DSP):c.667G>A(p.Gly223Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,614,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G223D) has been classified as Uncertain significance.
Frequency
Consequence
NM_004415.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.667G>A | p.Gly223Ser | missense_variant | 5/24 | ENST00000379802.8 | |
DSP | NM_001319034.2 | c.667G>A | p.Gly223Ser | missense_variant | 5/24 | ||
DSP | NM_001008844.3 | c.667G>A | p.Gly223Ser | missense_variant | 5/24 | ||
DSP | NM_001406591.1 | c.667G>A | p.Gly223Ser | missense_variant | 5/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.667G>A | p.Gly223Ser | missense_variant | 5/24 | 1 | NM_004415.4 | P2 | |
DSP | ENST00000418664.2 | c.667G>A | p.Gly223Ser | missense_variant | 5/24 | 1 | A2 | ||
DSP | ENST00000710359.1 | c.667G>A | p.Gly223Ser | missense_variant | 5/24 | A2 | |||
DSP | ENST00000506617.1 | n.185G>A | non_coding_transcript_exon_variant | 2/4 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152078Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251444Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135898
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461880Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727242
GnomAD4 genome ? AF: 0.0000986 AC: 15AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74414
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 14, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Arrhythmogenic right ventricular dysplasia 8;C1854063:Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Dec 29, 2019 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 07, 2017 | 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at