13-42127463-A-G

Variant names:

• chr13-42127463-A-G
• NM_178009.5:c.193A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178009.5(DGKH):​c.193A>G​(p.Thr65Ala) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DGKH NM_178009.5 missense, splice_region
• Scores: Splicing: ADA: 0.004358
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.31

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16704118).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKH	NM_178009.5	c.193A>G	p.Thr65Ala	missense_variant, splice_region_variant	Exon 2 of 30	ENST00000337343.9	NP_821077.1
DGKH	NM_001204504.3	c.193A>G	p.Thr65Ala	missense_variant, splice_region_variant	Exon 3 of 30		NP_001191433.1
DGKH	NM_152910.6	c.193A>G	p.Thr65Ala	missense_variant, splice_region_variant	Exon 2 of 29		NP_690874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKH	ENST00000337343.9	c.193A>G	p.Thr65Ala	missense_variant, splice_region_variant	Exon 2 of 30	1	NM_178009.5	ENSP00000337572.4
DGKH	ENST00000261491.9	c.193A>G	p.Thr65Ala	missense_variant, splice_region_variant	Exon 2 of 29	1		ENSP00000261491.4
DGKH	ENST00000379274.6	c.193A>G	p.Thr65Ala	missense_variant, splice_region_variant	Exon 3 of 30	2		ENSP00000368576.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457650 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 725396

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.020	.;T;.
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D;D;.
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.83	L;L;L
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.86	.;N;N
REVEL	Benign	0.23
Sift	Benign	0.37	.;T;T
Sift4G	Benign	0.75	T;T;T
Polyphen		0.94	P;B;P
Vest4		0.42
MutPred		0.26		Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);
MVP		0.53
MPC		0.73
ClinPred		0.84	D
GERP RS		5.5
Varity_R		0.20
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0044
dbscSNV1_RF	Benign	0.082
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-42701599;