chr13-42159329-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_178009.5(DGKH):c.686C>T(p.Thr229Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000178 in 1,497,420 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00020 ( 0 hom., cov: 29)
Exomes 𝑓: 0.00018 ( 0 hom. )
Consequence
DGKH
NM_178009.5 missense
NM_178009.5 missense
Scores
4
10
2
Clinical Significance
Conservation
PhyloP100: 7.57
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 -4 ACMG points.
BS2
?
High AC in GnomAd at 27 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DGKH | NM_178009.5 | c.686C>T | p.Thr229Ile | missense_variant | 6/30 | ENST00000337343.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DGKH | ENST00000337343.9 | c.686C>T | p.Thr229Ile | missense_variant | 6/30 | 1 | NM_178009.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000202 AC: 27AN: 133422Hom.: 0 Cov.: 29
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000294 AC: 74AN: 251338Hom.: 0 AF XY: 0.000317 AC XY: 43AN XY: 135844
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GnomAD4 exome AF: 0.000175 AC: 239AN: 1363928Hom.: 0 Cov.: 33 AF XY: 0.000217 AC XY: 147AN XY: 677974
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GnomAD4 genome ? AF: 0.000202 AC: 27AN: 133492Hom.: 0 Cov.: 29 AF XY: 0.000111 AC XY: 7AN XY: 63092
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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 | Jun 24, 2022 | The c.686C>T (p.T229I) alteration is located in exon 6 (coding exon 6) of the DGKH gene. This alteration results from a C to T substitution at nucleotide position 686, causing the threonine (T) at amino acid position 229 to be replaced by an isoleucine (I). 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
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;.;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;M;.;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
REVEL
Uncertain
Sift4G
Benign
T;D;T;D;D
Polyphen
D;D;D;.;D
Vest4
MVP
MPC
1.4
ClinPred
D
GERP RS
Varity_R
gMVP
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