rs9533040

Variant names:

• chr13-42222585-T-C
• rs9533040
• NM_178009.5:c.3573+1191T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.86).
• 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 rank	MANE	Protein	UniProt
DGKH	NM_178009.5	c.3573+1191T>C		intron_variant	Intron 29 of 29	ENST00000337343.9	NP_821077.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKH	ENST00000337343.9	c.3573+1191T>C		intron_variant	Intron 29 of 29	1	NM_178009.5	ENSP00000337572.4

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

African (AFR) AF: 0.0343 AC: 1423 AN: 41522

American (AMR) AF: 0.0869 AC: 1328 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 387 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.0232 AC: 112 AN: 4822

European-Finnish (FIN) AF: 0.0920 AC: 974 AN: 10586

Middle Eastern (MID) AF: 0.147 AC: 43 AN: 292

European-Non Finnish (NFE) AF: 0.119 AC: 8070 AN: 67942

Other (OTH) AF: 0.111 AC: 235 AN: 2112

Alfa AF: 0.113 Hom.: 1636

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
PhyloP100		0.13
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: rs9533040; hg19: chr13-42796721;