NM_178009.5:c.3213+376C>G

Variant names:

• chr13-42216043-C-G
• rs347405
• NM_178009.5:c.3213+376C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DGKH	NM_178009.5	c.3213+376C>G		intron_variant	Intron 26 of 29	ENST00000337343.9	NP_821077.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKH	ENST00000337343.9	c.3213+376C>G		intron_variant	Intron 26 of 29	1	NM_178009.5	ENSP00000337572.4

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

African (AFR) AF: 0.339 AC: 14074 AN: 41498

American (AMR) AF: 0.632 AC: 9660 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1808 AN: 3472

East Asian (EAS) AF: 0.761 AC: 3947 AN: 5184

South Asian (SAS) AF: 0.599 AC: 2890 AN: 4824

European-Finnish (FIN) AF: 0.607 AC: 6423 AN: 10590

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.537 AC: 36475 AN: 67986

Other (OTH) AF: 0.513 AC: 1084 AN: 2112

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
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs347405; hg19: chr13-42790179;