21-44258566-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_175867.3(DNMT3L):c.473G>A(p.Arg158Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000493 in 1,602,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_175867.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNMT3L | ENST00000628202.3 | c.473G>A | p.Arg158Lys | missense_variant | Exon 6 of 12 | 1 | NM_175867.3 | ENSP00000486001.1 | ||
DNMT3L | ENST00000270172.7 | c.473G>A | p.Arg158Lys | missense_variant | Exon 6 of 12 | 1 | ENSP00000270172.3 | |||
DNMT3L | ENST00000431166.1 | c.428G>A | p.Arg143Lys | missense_variant | Exon 5 of 9 | 5 | ENSP00000400242.1 |
Frequencies
GnomAD3 genomes AF: 0.000302 AC: 46AN: 152276Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000349 AC: 8AN: 229474Hom.: 0 AF XY: 0.0000240 AC XY: 3AN XY: 125074
GnomAD4 exome AF: 0.0000227 AC: 33AN: 1450586Hom.: 0 Cov.: 31 AF XY: 0.0000250 AC XY: 18AN XY: 720798
GnomAD4 genome AF: 0.000302 AC: 46AN: 152394Hom.: 0 Cov.: 32 AF XY: 0.000282 AC XY: 21AN XY: 74530
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.473G>A (p.R158K) alteration is located in exon 6 (coding exon 5) of the DNMT3L gene. This alteration results from a G to A substitution at nucleotide position 473, causing the arginine (R) at amino acid position 158 to be replaced by a lysine (K). 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