rs180870

Variant names:

• chr13-42219343-G-A
• rs180870
• NM_178009.5:c.3327G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-42219343-G-A
• chr13-42219343-G-C
• chr13-42219343-G-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_178009.5(DGKH):​c.3327G>A​(p.Glu1109Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 1,612,736 control chromosomes in the GnomAD database, including 358,502 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 0.65 (32614 hom., cov: 32)
  • Exomes 𝑓: 0.67 (325888 hom.)
• Consequence: DGKH NM_178009.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230
• Publications: 19 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=0.23 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 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.3327G>A	p.Glu1109Glu	synonymous	Exon 27 of 30	NP_821077.1	Q86XP1-1
	DGKH	NM_001204504.3		c.3327G>A	p.Glu1109Glu	synonymous	Exon 28 of 30	NP_001191433.1	Q86XP1-2
	DGKH	NM_152910.6		c.3327G>A	p.Glu1109Glu	synonymous	Exon 27 of 29	NP_690874.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKH	ENST00000337343.9	TSL:1 MANE Select	c.3327G>A	p.Glu1109Glu	synonymous	Exon 27 of 30	ENSP00000337572.4	Q86XP1-1
	DGKH	ENST00000261491.9	TSL:1	c.3327G>A	p.Glu1109Glu	synonymous	Exon 27 of 29	ENSP00000261491.4	Q86XP1-2
	DGKH	ENST00000536612.3	TSL:1	c.2919G>A	p.Glu973Glu	synonymous	Exon 25 of 29	ENSP00000445114.2	Q86XP1-3

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99240 AN: 151944 Hom.: 32598 Cov.: 32

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.685

GnomAD2 exomes AF: 0.642 AC: 160810 AN: 250580 AF XY: 0.638

Gnomad AFR exome AF: 0.616

Gnomad AMR exome AF: 0.573

Gnomad ASJ exome AF: 0.669

Gnomad EAS exome AF: 0.766

Gnomad FIN exome AF: 0.690

Gnomad NFE exome AF: 0.675

Gnomad OTH exome AF: 0.639

GnomAD4 exome AF: 0.666 AC: 972170 AN: 1460674 Hom.: 325888 Cov.: 45 AF XY: 0.661 AC XY: 480024 AN XY: 726712

African (AFR) AF: 0.614 AC: 20548 AN: 33448

American (AMR) AF: 0.576 AC: 25728 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 17387 AN: 26108

East Asian (EAS) AF: 0.743 AC: 29460 AN: 39668

South Asian (SAS) AF: 0.494 AC: 42536 AN: 86120

European-Finnish (FIN) AF: 0.690 AC: 36810 AN: 53360

Middle Eastern (MID) AF: 0.607 AC: 3493 AN: 5758

European-Non Finnish (NFE) AF: 0.681 AC: 756888 AN: 1111204

Other (OTH) AF: 0.652 AC: 39320 AN: 60342

GnomAD4 genome AF: 0.653 AC: 99295 AN: 152062 Hom.: 32614 Cov.: 32 AF XY: 0.652 AC XY: 48409 AN XY: 74300

African (AFR) AF: 0.614 AC: 25450 AN: 41462

American (AMR) AF: 0.635 AC: 9707 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 2305 AN: 3470

East Asian (EAS) AF: 0.751 AC: 3885 AN: 5170

South Asian (SAS) AF: 0.498 AC: 2397 AN: 4816

European-Finnish (FIN) AF: 0.695 AC: 7340 AN: 10566

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45909 AN: 67980

Other (OTH) AF: 0.685 AC: 1447 AN: 2112

Alfa AF: 0.668 Hom.: 66929

Bravo AF: 0.653

Asia WGS AF: 0.627 AC: 2180 AN: 3478

EpiCase AF: 0.675

EpiControl AF: 0.670

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	5.8
DANN	Benign	0.58
PhyloP100		0.23
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: rs180870; hg19: chr13-42793479; COSMIC: COSV54932190; COSMIC: COSV54932190;