13-42101357-A-G

Variant names:

• chr13-42101357-A-G
• rs1170191
• NM_178009.5:c.193-26106A>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.193-26106A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 152,214 control chromosomes in the GnomAD database, including 50,185 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 0.81 (50185 hom., cov: 33)
• Consequence: DGKH NM_178009.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.676
• Publications: 21 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKH	NM_178009.5	c.193-26106A>G		intron_variant	Intron 1 of 29	ENST00000337343.9	NP_821077.1
DGKH	NM_001204504.3	c.193-26106A>G		intron_variant	Intron 2 of 29		NP_001191433.1
DGKH	NM_152910.6	c.193-26106A>G		intron_variant	Intron 1 of 28		NP_690874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKH	ENST00000337343.9	c.193-26106A>G		intron_variant	Intron 1 of 29	1	NM_178009.5	ENSP00000337572.4
DGKH	ENST00000261491.9	c.193-26106A>G		intron_variant	Intron 1 of 28	1		ENSP00000261491.4
DGKH	ENST00000379274.6	c.193-26106A>G		intron_variant	Intron 2 of 29	2		ENSP00000368576.3

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122854 AN: 152096 Hom.: 50131 Cov.: 33

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.802

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

GnomAD4 genome AF: 0.808 AC: 122968 AN: 152214 Hom.: 50185 Cov.: 33 AF XY: 0.801 AC XY: 59593 AN XY: 74406

African (AFR) AF: 0.893 AC: 37098 AN: 41556

American (AMR) AF: 0.726 AC: 11108 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2281 AN: 3470

East Asian (EAS) AF: 0.539 AC: 2791 AN: 5182

South Asian (SAS) AF: 0.719 AC: 3473 AN: 4832

European-Finnish (FIN) AF: 0.761 AC: 8038 AN: 10562

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.817 AC: 55582 AN: 68006

Other (OTH) AF: 0.805 AC: 1696 AN: 2108

Alfa AF: 0.804 Hom.: 215080

Bravo AF: 0.805

Asia WGS AF: 0.682 AC: 2375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.10
DANN	Benign	0.29
PhyloP100		-0.68
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: rs1170191; hg19: chr13-42675493;