rs17646069

Variant names:

• chr13-42229127-T-C
• rs17646069
• NM_178009.5:c.3602T>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.3602T>C​(p.Val1201Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0345 in 1,611,378 control chromosomes in the GnomAD database, including 1,468 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 0.029 (110 hom., cov: 33)
  • Exomes 𝑓: 0.035 (1358 hom.)
• Consequence: DGKH NM_178009.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.18
• Publications: 17 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 (MetaRNN=0.0021175146).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKH	NM_178009.5	c.3602T>C	p.Val1201Ala	missense_variant	Exon 30 of 30	ENST00000337343.9	NP_821077.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKH	ENST00000337343.9	c.3602T>C	p.Val1201Ala	missense_variant	Exon 30 of 30	1	NM_178009.5	ENSP00000337572.4

Frequencies

GnomAD3 genomes AF: 0.0293 AC: 4458 AN: 152152 Hom.: 109 Cov.: 33

Gnomad AFR AF: 0.00598

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0371

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.0806

Gnomad FIN AF: 0.0363

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0278

Gnomad OTH AF: 0.0239

GnomAD2 exomes AF: 0.0446 AC: 11083 AN: 248758 AF XY: 0.0452

Gnomad AFR exome AF: 0.00576

Gnomad AMR exome AF: 0.0545

Gnomad ASJ exome AF: 0.0301

Gnomad EAS exome AF: 0.136

Gnomad FIN exome AF: 0.0346

Gnomad NFE exome AF: 0.0288

Gnomad OTH exome AF: 0.0358

GnomAD4 exome AF: 0.0350 AC: 51119 AN: 1459106 Hom.: 1358 Cov.: 31 AF XY: 0.0360 AC XY: 26107 AN XY: 725728

African (AFR) AF: 0.00511 AC: 170 AN: 33288

American (AMR) AF: 0.0497 AC: 2197 AN: 44176

Ashkenazi Jewish (ASJ) AF: 0.0286 AC: 746 AN: 26080

East Asian (EAS) AF: 0.143 AC: 5630 AN: 39508

South Asian (SAS) AF: 0.0740 AC: 6322 AN: 85470

European-Finnish (FIN) AF: 0.0347 AC: 1851 AN: 53364

Middle Eastern (MID) AF: 0.0245 AC: 141 AN: 5762

European-Non Finnish (NFE) AF: 0.0288 AC: 31962 AN: 1111166

Other (OTH) AF: 0.0348 AC: 2100 AN: 60292

GnomAD4 genome AF: 0.0293 AC: 4456 AN: 152272 Hom.: 110 Cov.: 33 AF XY: 0.0316 AC XY: 2351 AN XY: 74462

African (AFR) AF: 0.00597 AC: 248 AN: 41574

American (AMR) AF: 0.0370 AC: 565 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3472

East Asian (EAS) AF: 0.148 AC: 766 AN: 5176

South Asian (SAS) AF: 0.0815 AC: 393 AN: 4824

European-Finnish (FIN) AF: 0.0363 AC: 385 AN: 10612

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0278 AC: 1891 AN: 68006

Other (OTH) AF: 0.0232 AC: 49 AN: 2112

Alfa AF: 0.0312 Hom.: 457

Bravo AF: 0.0289

TwinsUK AF: 0.0245 AC: 91

ALSPAC AF: 0.0278 AC: 107

ESP6500AA AF: 0.00658 AC: 29

ESP6500EA AF: 0.0280 AC: 241

ExAC AF: 0.0447 AC: 5423

Asia WGS AF: 0.0850 AC: 294 AN: 3478

EpiCase AF: 0.0280

EpiControl AF: 0.0258

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	D;D;D
MetaRNN	Benign	0.0021	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.16	N;.;.
PhyloP100		5.2
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.6	N;.;.
REVEL	Uncertain	0.34
Sift	Uncertain	0.0070	D;.;.
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		0.29	B;.;B
Vest4		0.094
MPC		0.67
ClinPred		0.026	T
GERP RS		5.9
Varity_R		0.31
gMVP		0.39
Mutation Taster		=60/40	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: rs17646069; hg19: chr13-42803263; COSMIC: COSV54932494;