13-42160758-T-C

Variant names:

• chr13-42160758-T-C
• rs9525584
• NM_178009.5:c.855+622T>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.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
• Publications: 8 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178009.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKH	NM_178009.5	MANE Select	c.855+622T>C		intron	N/A	NP_821077.1
	DGKH	NM_001204504.3		c.855+622T>C		intron	N/A	NP_001191433.1
	DGKH	NM_152910.6		c.855+622T>C		intron	N/A	NP_690874.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKH	ENST00000337343.9	TSL:1 MANE Select	c.855+622T>C		intron	N/A	ENSP00000337572.4
	DGKH	ENST00000261491.9	TSL:1	c.855+622T>C		intron	N/A	ENSP00000261491.4
	DGKH	ENST00000536612.3	TSL:1	c.447+622T>C		intron	N/A	ENSP00000445114.2

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

African (AFR) AF: 0.583 AC: 24161 AN: 41456

American (AMR) AF: 0.307 AC: 4688 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1192 AN: 3470

East Asian (EAS) AF: 0.253 AC: 1312 AN: 5180

South Asian (SAS) AF: 0.272 AC: 1310 AN: 4820

European-Finnish (FIN) AF: 0.451 AC: 4764 AN: 10566

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30178 AN: 67976

Other (OTH) AF: 0.432 AC: 912 AN: 2112

Alfa AF: 0.440 Hom.: 7889

Bravo AF: 0.449

Asia WGS AF: 0.302 AC: 1051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.044
DANN	Benign	0.39
PhyloP100		-0.56
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: rs9525584; hg19: chr13-42734894;