rs347405

chr13-42216043-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178009.5(DGKH):c.3213+376C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 152,158 control chromosomes in the GnomAD database, including 20,484 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (20484 hom., cov: 33)
• Consequence: DGKH NM_178009.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGKH	NM_178009.5	c.3213+376C>G		intron_variant		ENST00000337343.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKH	ENST00000337343.9	c.3213+376C>G		intron_variant		1	NM_178009.5	P1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76893 AN: 152040 Hom.: 20465 Cov.: 33

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.513

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.506 AC: 76941 AN: 152158 Hom.: 20484 Cov.: 33 AF XY: 0.515 AC XY: 38305 AN XY: 74394

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.761

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.537

Gnomad4 OTH AF: 0.513

Alfa AF: 0.520 Hom.: 2637

Bravo AF: 0.502

Asia WGS AF: 0.661 AC: 2298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.2
Dann	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
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

LitVar

Other links and lift over

dbSNP: rs347405; hg19: chr13-42790179;