13-42068674-C-T

Position:

• chr13-42068674-C-T

Variant summary

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

The NM_178009.5(DGKH):​c.192+19709C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 151,932 control chromosomes in the GnomAD database, including 29,720 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 0.62 (29720 hom., cov: 32)
• Consequence: DGKH NM_178009.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359

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=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKH	NM_178009.5	c.192+19709C>T		intron_variant		ENST00000337343.9	NP_821077.1
DGKH	NM_001204504.3	c.192+19709C>T		intron_variant			NP_001191433.1
DGKH	NM_152910.6	c.192+19709C>T		intron_variant			NP_690874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKH	ENST00000337343.9	c.192+19709C>T		intron_variant		1	NM_178009.5	ENSP00000337572	P1
DGKH	ENST00000261491.9	c.192+19709C>T		intron_variant		1		ENSP00000261491
DGKH	ENST00000379274.6	c.192+19709C>T		intron_variant		2		ENSP00000368576

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94485 AN: 151814 Hom.: 29692 Cov.: 32

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.622 AC: 94549 AN: 151932 Hom.: 29720 Cov.: 32 AF XY: 0.618 AC XY: 45903 AN XY: 74236

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.630

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.604

Alfa AF: 0.648 Hom.: 6054

Bravo AF: 0.612

Asia WGS AF: 0.585 AC: 2036 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	9.7
DANN	Benign	0.61

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: rs9315885; hg19: chr13-42642810;