rs994856

Variant names:

• chr13-42134315-A-G
• rs994856
• NM_178009.5:c.384+4683A>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.384+4683A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,054 control chromosomes in the GnomAD database, including 11,327 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 0.37 (11327 hom., cov: 32)
• Consequence: DGKH NM_178009.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52
• Publications: 9 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKH	NM_178009.5	c.384+4683A>G		intron_variant	Intron 3 of 29	ENST00000337343.9	NP_821077.1
DGKH	NM_001204504.3	c.384+4683A>G		intron_variant	Intron 4 of 29		NP_001191433.1
DGKH	NM_152910.6	c.384+4683A>G		intron_variant	Intron 3 of 28		NP_690874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKH	ENST00000337343.9	c.384+4683A>G		intron_variant	Intron 3 of 29	1	NM_178009.5	ENSP00000337572.4
DGKH	ENST00000261491.9	c.384+4683A>G		intron_variant	Intron 3 of 28	1		ENSP00000261491.4
DGKH	ENST00000379274.6	c.384+4683A>G		intron_variant	Intron 4 of 29	2		ENSP00000368576.3

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56884 AN: 151936 Hom.: 11309 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.375 AC: 56950 AN: 152054 Hom.: 11327 Cov.: 32 AF XY: 0.376 AC XY: 27919 AN XY: 74326

African (AFR) AF: 0.249 AC: 10328 AN: 41486

American (AMR) AF: 0.444 AC: 6790 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1453 AN: 3472

East Asian (EAS) AF: 0.186 AC: 963 AN: 5172

South Asian (SAS) AF: 0.455 AC: 2195 AN: 4820

European-Finnish (FIN) AF: 0.399 AC: 4213 AN: 10570

Middle Eastern (MID) AF: 0.384 AC: 112 AN: 292

European-Non Finnish (NFE) AF: 0.438 AC: 29735 AN: 67944

Other (OTH) AF: 0.396 AC: 836 AN: 2110

Alfa AF: 0.409 Hom.: 5455

Bravo AF: 0.372

Asia WGS AF: 0.311 AC: 1083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.011
DANN	Benign	0.35
PhyloP100		-2.5
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: rs994856; hg19: chr13-42708451;