chr13-42127524-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_178009.5(DGKH):c.254G>T(p.Arg85Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000508 in 1,613,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging 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. R85P) has been classified as Uncertain significance.
Frequency
Consequence
NM_178009.5 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 |
---|---|---|---|---|---|---|---|
DGKH | NM_178009.5 | c.254G>T | p.Arg85Leu | missense_variant | 2/30 | ENST00000337343.9 | |
DGKH | NM_001204504.3 | c.254G>T | p.Arg85Leu | missense_variant | 3/30 | ||
DGKH | NM_152910.6 | c.254G>T | p.Arg85Leu | missense_variant | 2/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DGKH | ENST00000337343.9 | c.254G>T | p.Arg85Leu | missense_variant | 2/30 | 1 | NM_178009.5 | P1 | |
DGKH | ENST00000261491.9 | c.254G>T | p.Arg85Leu | missense_variant | 2/29 | 1 | |||
DGKH | ENST00000379274.6 | c.254G>T | p.Arg85Leu | missense_variant | 3/30 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152100Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251226Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135780
GnomAD4 exome AF: 0.0000554 AC: 81AN: 1461560Hom.: 0 Cov.: 31 AF XY: 0.0000646 AC XY: 47AN XY: 727086
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152100Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74300
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 02, 2021 | The c.254G>T (p.R85L) alteration is located in exon 2 (coding exon 2) of the DGKH gene. This alteration results from a G to T substitution at nucleotide position 254, causing the arginine (R) at amino acid position 85 to be replaced by a leucine (L). 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