chr18-31001626-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001941.5(DSC3):c.2227G>A(p.Asp743Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000559 in 1,609,370 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D743V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001941.5 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 |
---|---|---|---|---|---|---|---|
DSC3 | NM_001941.5 | c.2227G>A | p.Asp743Asn | missense_variant | 14/16 | ENST00000360428.9 | |
DSC3 | NM_024423.4 | c.2227G>A | p.Asp743Asn | missense_variant | 14/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSC3 | ENST00000360428.9 | c.2227G>A | p.Asp743Asn | missense_variant | 14/16 | 1 | NM_001941.5 | P1 | |
DSC3 | ENST00000434452.5 | c.2227G>A | p.Asp743Asn | missense_variant | 14/17 | 5 | |||
DSC3 | ENST00000584980.1 | c.352G>A | p.Asp118Asn | missense_variant | 3/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152056Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250704Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135520
GnomAD4 exome AF: 0.00000549 AC: 8AN: 1457314Hom.: 0 Cov.: 30 AF XY: 0.00000690 AC XY: 5AN XY: 724906
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152056Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74274
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 13, 2022 | The c.2227G>A (p.D743N) alteration is located in exon 14 (coding exon 14) of the DSC3 gene. This alteration results from a G to A substitution at nucleotide position 2227, causing the aspartic acid (D) at amino acid position 743 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at