chr6-7568478-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004415.4(DSP):c.1308G>C(p.Gln436His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Q436Q) has been classified as Likely benign.
Frequency
Consequence
NM_004415.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.1308G>C | p.Gln436His | missense_variant | 11/24 | ENST00000379802.8 | |
DSP | NM_001319034.2 | c.1308G>C | p.Gln436His | missense_variant | 11/24 | ||
DSP | NM_001008844.3 | c.1308G>C | p.Gln436His | missense_variant | 11/24 | ||
DSP | NM_001406591.1 | c.1308G>C | p.Gln436His | missense_variant | 11/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.1308G>C | p.Gln436His | missense_variant | 11/24 | 1 | NM_004415.4 | P2 | |
DSP | ENST00000418664.2 | c.1308G>C | p.Gln436His | missense_variant | 11/24 | 1 | A2 | ||
DSP | ENST00000710359.1 | c.1308G>C | p.Gln436His | missense_variant | 11/24 | A2 | |||
DSP | ENST00000682228.1 | n.1493G>C | non_coding_transcript_exon_variant | 3/3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461812Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727200
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Arrhythmogenic right ventricular dysplasia 8;C1854063:Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2018 | Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with DSP-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with histidine at codon 436 of the DSP protein (p.Gln436His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at