NM_178009.5:c.193-3760A>G

Variant names:

• chr13-42123703-A-G
• rs2148004
• NM_178009.5:c.193-3760A>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.193-3760A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,198 control chromosomes in the GnomAD database, including 5,473 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 0.26 (5473 hom., cov: 33)
• Consequence: DGKH NM_178009.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.755
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178009.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKH	NM_178009.5	MANE Select	c.193-3760A>G		intron	N/A	NP_821077.1	Q86XP1-1
	DGKH	NM_001204504.3		c.193-3760A>G		intron	N/A	NP_001191433.1	Q86XP1-2
	DGKH	NM_152910.6		c.193-3760A>G		intron	N/A	NP_690874.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKH	ENST00000337343.9	TSL:1 MANE Select	c.193-3760A>G		intron	N/A	ENSP00000337572.4	Q86XP1-1
	DGKH	ENST00000261491.9	TSL:1	c.193-3760A>G		intron	N/A	ENSP00000261491.4	Q86XP1-2
	DGKH	ENST00000916518.1		c.193-3760A>G		intron	N/A	ENSP00000586577.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40322 AN: 152080 Hom.: 5472 Cov.: 33

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.265 AC: 40331 AN: 152198 Hom.: 5473 Cov.: 33 AF XY: 0.261 AC XY: 19446 AN XY: 74424

African (AFR) AF: 0.247 AC: 10240 AN: 41522

American (AMR) AF: 0.194 AC: 2973 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 700 AN: 3468

East Asian (EAS) AF: 0.247 AC: 1277 AN: 5176

South Asian (SAS) AF: 0.159 AC: 765 AN: 4826

European-Finnish (FIN) AF: 0.300 AC: 3180 AN: 10604

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20237 AN: 67996

Other (OTH) AF: 0.283 AC: 597 AN: 2112

Alfa AF: 0.280 Hom.: 7911

Bravo AF: 0.261

Asia WGS AF: 0.221 AC: 770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.0
DANN	Benign	0.54
PhyloP100		0.76
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: rs2148004; hg19: chr13-42697839;