NM_001374736.1:c.4330G>A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_001374736.1(DST):c.4330G>A(p.Glu1444Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,613,618 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001374736.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DST | ENST00000680361.1 | c.4330G>A | p.Glu1444Lys | missense_variant | Exon 32 of 104 | NM_001374736.1 | ENSP00000505098.1 | |||
DST | ENST00000370765.11 | c.2719G>A | p.Glu907Lys | missense_variant | Exon 18 of 24 | 1 | NM_001723.7 | ENSP00000359801.6 |
Frequencies
GnomAD3 genomes AF: 0.000335 AC: 51AN: 152156Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000661 AC: 166AN: 251270Hom.: 0 AF XY: 0.000611 AC XY: 83AN XY: 135806
GnomAD4 exome AF: 0.000138 AC: 201AN: 1461344Hom.: 0 Cov.: 31 AF XY: 0.000144 AC XY: 105AN XY: 726984
GnomAD4 genome AF: 0.000335 AC: 51AN: 152274Hom.: 0 Cov.: 32 AF XY: 0.000457 AC XY: 34AN XY: 74454
ClinVar
Submissions by phenotype
not provided Uncertain:1
Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported using the transcript encoding the epithelial isoform of the gene. -
Hereditary sensory and autonomic neuropathy type 6;C3809470:Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency Benign:1
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Inborn genetic diseases Benign:1
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