21-44258534-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_175867.3(DNMT3L):c.505G>A(p.Asp169Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000159 in 1,574,422 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNMT3L | ENST00000628202.3 | c.505G>A | p.Asp169Asn | missense_variant | Exon 6 of 12 | 1 | NM_175867.3 | ENSP00000486001.1 | ||
DNMT3L | ENST00000270172.7 | c.505G>A | p.Asp169Asn | missense_variant | Exon 6 of 12 | 1 | ENSP00000270172.3 | |||
DNMT3L | ENST00000431166.1 | c.460G>A | p.Asp154Asn | missense_variant | Exon 5 of 9 | 5 | ENSP00000400242.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152264Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000688 AC: 13AN: 188936Hom.: 1 AF XY: 0.0000391 AC XY: 4AN XY: 102390
GnomAD4 exome AF: 0.0000162 AC: 23AN: 1422158Hom.: 1 Cov.: 31 AF XY: 0.00000994 AC XY: 7AN XY: 704234
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152264Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74386
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.505G>A (p.D169N) 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 505, causing the aspartic acid (D) at amino acid position 169 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