rs397516912
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_004415.4(DSP):āc.1112A>Cā(p.His371Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H371L) has been classified as Uncertain significance.
Frequency
Consequence
NM_004415.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.1112A>C | p.His371Pro | missense_variant | 9/24 | ENST00000379802.8 | |
DSP | NM_001319034.2 | c.1112A>C | p.His371Pro | missense_variant | 9/24 | ||
DSP | NM_001008844.3 | c.1112A>C | p.His371Pro | missense_variant | 9/24 | ||
DSP | NM_001406591.1 | c.1112A>C | p.His371Pro | missense_variant | 9/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.1112A>C | p.His371Pro | missense_variant | 9/24 | 1 | NM_004415.4 | P2 | |
DSP | ENST00000418664.2 | c.1112A>C | p.His371Pro | missense_variant | 9/24 | 1 | A2 | ||
DSP | ENST00000710359.1 | c.1112A>C | p.His371Pro | missense_variant | 9/24 | A2 | |||
DSP | ENST00000682228.1 | n.436A>C | non_coding_transcript_exon_variant | 3/3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461778Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727198
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 22, 2012 | The His371Pro variant (DSP) has not been reported in the literature nor previous ly identified by our laboratory. Variants in DSP have been reported in individu als with ARVC. Computational analyses (biochemical amino acid properties, conse rvation, AlignGVGD, PolyPhen2, and SIFT) suggest that this variant may impact th e protein, though this information is not predictive enough to determine pathoge nicity. Additional studies are needed to fully assess its clinical significance. - |
Arrhythmogenic right ventricular dysplasia 8;C1854063:Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 24, 2016 | 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"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a DSP-related disease. ClinVar contains an entry for this variant (Variation ID: 44851). This sequence change replaces histidine with proline at codon 371 of the DSP protein (p.His371Pro). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and proline. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at