chr13-42166608-G-A
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_178009.5(DGKH):c.1052G>A(p.Arg351His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000746 in 1,608,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000076 ( 0 hom. )
Consequence
DGKH
NM_178009.5 missense
NM_178009.5 missense
Scores
7
5
4
Clinical Significance
Conservation
PhyloP100: 10.0
Genes affected
DGKH (HGNC:2854): (diacylglycerol kinase eta) This gene encodes a member of the diacylglycerol kinase (DGK) enzyme family. Members of this family are involved in regulating intracellular concentrations of diacylglycerol and phosphatidic acid. Variation in this gene has been associated with bipolar disorder. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Jul 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.819
BS2
High AC in GnomAdExome4 at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DGKH | NM_178009.5 | c.1052G>A | p.Arg351His | missense_variant | 9/30 | ENST00000337343.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DGKH | ENST00000337343.9 | c.1052G>A | p.Arg351His | missense_variant | 9/30 | 1 | NM_178009.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152000Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000121 AC: 3AN: 247212Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 133792
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GnomAD4 exome AF: 0.00000755 AC: 11AN: 1456652Hom.: 0 Cov.: 30 AF XY: 0.00000966 AC XY: 7AN XY: 724602
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 152000Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74262
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 08, 2022 | The c.1052G>A (p.R351H) alteration is located in exon 9 (coding exon 9) of the DGKH gene. This alteration results from a G to A substitution at nucleotide position 1052, causing the arginine (R) at amino acid position 351 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;.;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;.;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Pathogenic
D
REVEL
Uncertain
Sift4G
Pathogenic
D;D;D;D;D
Polyphen
D;D;D;.;D
Vest4
MutPred
Loss of MoRF binding (P = 0.0157);Loss of MoRF binding (P = 0.0157);Loss of MoRF binding (P = 0.0157);.;.;
MVP
MPC
1.5
ClinPred
D
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at