13-42180386-T-C

Variant names:

• chr13-42180386-T-C
• rs4142110
• NM_178009.5:c.1538+2166T>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.1538+2166T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,106 control chromosomes in the GnomAD database, including 10,402 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 0.34 (10402 hom., cov: 32)
• Consequence: DGKH NM_178009.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201
• Publications: 19 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.504 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKH	NM_178009.5	MANE Select	c.1538+2166T>C		intron	N/A	NP_821077.1	Q86XP1-1
	DGKH	NM_001204504.3		c.1538+2166T>C		intron	N/A	NP_001191433.1	Q86XP1-2
	DGKH	NM_152910.6		c.1538+2166T>C		intron	N/A	NP_690874.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKH	ENST00000337343.9	TSL:1 MANE Select	c.1538+2166T>C		intron	N/A	ENSP00000337572.4	Q86XP1-1
	DGKH	ENST00000261491.9	TSL:1	c.1538+2166T>C		intron	N/A	ENSP00000261491.4	Q86XP1-2
	DGKH	ENST00000536612.3	TSL:1	c.1130+2166T>C		intron	N/A	ENSP00000445114.2	Q86XP1-3

Frequencies

GnomAD3 genomes AF: 0.342 AC: 52032 AN: 151988 Hom.: 10380 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.342 AC: 52066 AN: 152106 Hom.: 10402 Cov.: 32 AF XY: 0.351 AC XY: 26122 AN XY: 74360

African (AFR) AF: 0.142 AC: 5905 AN: 41514

American (AMR) AF: 0.511 AC: 7802 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1626 AN: 3472

East Asian (EAS) AF: 0.520 AC: 2697 AN: 5182

South Asian (SAS) AF: 0.450 AC: 2163 AN: 4810

European-Finnish (FIN) AF: 0.445 AC: 4696 AN: 10548

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26086 AN: 67982

Other (OTH) AF: 0.335 AC: 709 AN: 2114

Alfa AF: 0.379 Hom.: 48838

Bravo AF: 0.342

Asia WGS AF: 0.434 AC: 1510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.52
PhyloP100		-0.20
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: rs4142110; hg19: chr13-42754522; COSMIC: COSV54940250; COSMIC: COSV54940250;