13-42104835-A-G

Position:

• chr13-42104835-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178009.5(DGKH):​c.193-22628A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 152,132 control chromosomes in the GnomAD database, including 50,665 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 (50665 hom., cov: 31)
• Consequence: DGKH NM_178009.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGKH	NM_178009.5	c.193-22628A>G		intron_variant		ENST00000337343.9
DGKH	NM_001204504.3	c.193-22628A>G		intron_variant
DGKH	NM_152910.6	c.193-22628A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKH	ENST00000337343.9	c.193-22628A>G		intron_variant		1	NM_178009.5	P1
DGKH	ENST00000261491.9	c.193-22628A>G		intron_variant		1
DGKH	ENST00000379274.6	c.193-22628A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.811 AC: 123337 AN: 152014 Hom.: 50612 Cov.: 31

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.802

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

GnomAD4 genome AF: 0.811 AC: 123450 AN: 152132 Hom.: 50665 Cov.: 31 AF XY: 0.805 AC XY: 59811 AN XY: 74328

Gnomad4 AFR AF: 0.908

Gnomad4 AMR AF: 0.728

Gnomad4 ASJ AF: 0.657

Gnomad4 EAS AF: 0.538

Gnomad4 SAS AF: 0.720

Gnomad4 FIN AF: 0.760

Gnomad4 NFE AF: 0.816

Gnomad4 OTH AF: 0.805

Alfa AF: 0.808 Hom.: 8061

Bravo AF: 0.809

Asia WGS AF: 0.683 AC: 2378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs1170188; hg19: chr13-42678971;