chr13-42160758-T-C

Position:

• chr13-42160758-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.855+622T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 152,072 control chromosomes in the GnomAD database, including 16,500 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 0.45 (16500 hom., cov: 32)
• Consequence: DGKH NM_178009.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.565

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKH	NM_178009.5	c.855+622T>C		intron_variant		ENST00000337343.9	NP_821077.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKH	ENST00000337343.9	c.855+622T>C		intron_variant		1	NM_178009.5	ENSP00000337572	P1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69088 AN: 151954 Hom.: 16492 Cov.: 32

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.454 AC: 69116 AN: 152072 Hom.: 16500 Cov.: 32 AF XY: 0.447 AC XY: 33255 AN XY: 74368

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.432

Alfa AF: 0.439 Hom.: 7009

Bravo AF: 0.449

Asia WGS AF: 0.302 AC: 1051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.044
DANN	Benign	0.39

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: rs9525584; hg19: chr13-42734894;