chr8-42375773-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_014420.3(DKK4):c.169C>T(p.Arg57Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000632 in 1,614,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 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. R57H) has been classified as Likely benign.
Frequency
Consequence
NM_014420.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DKK4 | NM_014420.3 | c.169C>T | p.Arg57Cys | missense_variant | 2/4 | ENST00000220812.3 | |
DKK4 | XM_011544488.3 | c.169C>T | p.Arg57Cys | missense_variant | 3/5 | ||
DKK4 | XM_017013316.2 | c.169C>T | p.Arg57Cys | missense_variant | 3/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DKK4 | ENST00000220812.3 | c.169C>T | p.Arg57Cys | missense_variant | 2/4 | 1 | NM_014420.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000289 AC: 44AN: 152160Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000169 AC: 42AN: 248884Hom.: 0 AF XY: 0.000119 AC XY: 16AN XY: 134730
GnomAD4 exome AF: 0.0000397 AC: 58AN: 1461830Hom.: 0 Cov.: 31 AF XY: 0.0000358 AC XY: 26AN XY: 727204
GnomAD4 genome ? AF: 0.000289 AC: 44AN: 152278Hom.: 0 Cov.: 32 AF XY: 0.000390 AC XY: 29AN XY: 74442
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 19, 2022 | The c.169C>T (p.R57C) alteration is located in exon 2 (coding exon 2) of the DKK4 gene. This alteration results from a C to T substitution at nucleotide position 169, causing the arginine (R) at amino acid position 57 to be replaced by a cysteine (C). 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