rs9533040

chr13-42222585-T-C

Variant summary

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

The NM_178009.5(DGKH):c.3573+1191T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0833 in 152,114 control chromosomes in the GnomAD database, including 645 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 0.083 (645 hom., cov: 32)
• Consequence: DGKH NM_178009.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGKH	NM_178009.5	c.3573+1191T>C		intron_variant		ENST00000337343.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKH	ENST00000337343.9	c.3573+1191T>C		intron_variant		1	NM_178009.5	P1

Frequencies

GnomAD3 genomes AF: 0.0835 AC: 12685 AN: 151998 Hom.: 645 Cov.: 32

Gnomad AFR AF: 0.0344

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0871

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0236

Gnomad FIN AF: 0.0920

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.0833 AC: 12674 AN: 152114 Hom.: 645 Cov.: 32 AF XY: 0.0805 AC XY: 5986 AN XY: 74362

Gnomad4 AFR AF: 0.0343

Gnomad4 AMR AF: 0.0869

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0232

Gnomad4 FIN AF: 0.0920

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.111

Alfa AF: 0.116 Hom.: 1387

Bravo AF: 0.0843

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	5.3
Dann	Benign	0.70

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: rs9533040; hg19: chr13-42796721;