13-42100870-T-C

Position:

• chr13-42100870-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.193-26593T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,234 control chromosomes in the GnomAD database, including 1,592 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 0.14 (1592 hom., cov: 32)
• Consequence: DGKH NM_178009.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600

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=-0.55).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKH	NM_178009.5	c.193-26593T>C		intron_variant		ENST00000337343.9	NP_821077.1
DGKH	NM_001204504.3	c.193-26593T>C		intron_variant			NP_001191433.1
DGKH	NM_152910.6	c.193-26593T>C		intron_variant			NP_690874.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKH	ENST00000337343.9	c.193-26593T>C		intron_variant		1	NM_178009.5	ENSP00000337572.4
DGKH	ENST00000261491.9	c.193-26593T>C		intron_variant		1		ENSP00000261491.4
DGKH	ENST00000379274.6	c.193-26593T>C		intron_variant		2		ENSP00000368576.3

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20604 AN: 152116 Hom.: 1590 Cov.: 32

Gnomad AFR AF: 0.0848

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0868

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.0991

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.135 AC: 20622 AN: 152234 Hom.: 1592 Cov.: 32 AF XY: 0.135 AC XY: 10028 AN XY: 74450

Gnomad4 AFR AF: 0.0850

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.0866

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.0991

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.176

Alfa AF: 0.168 Hom.: 2923

Bravo AF: 0.138

Asia WGS AF: 0.132 AC: 459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Benign	0.94

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: rs9525570; hg19: chr13-42675006;