rs17646069

Positions:

• chr13-42229127-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.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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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]

DGKH (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
DGKH	NM_178009.5	c.3602T>C	p.Val1201Ala	missense_variant	30/30	ENST00000337343.9	NP_821077.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKH	ENST00000337343.9	c.3602T>C	p.Val1201Ala	missense_variant	30/30	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

GnomAD3 exomes AF: 0.0446 AC: 11083 AN: 248758 Hom.: 357 AF XY: 0.0452 AC XY: 6076 AN XY: 134468

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 SAS exome AF: 0.0723

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

Gnomad4 AFR exome AF: 0.00511

Gnomad4 AMR exome AF: 0.0497

Gnomad4 ASJ exome AF: 0.0286

Gnomad4 EAS exome AF: 0.143

Gnomad4 SAS exome AF: 0.0740

Gnomad4 FIN exome AF: 0.0347

Gnomad4 NFE exome AF: 0.0288

Gnomad4 OTH exome AF: 0.0348

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

Gnomad4 AFR AF: 0.00597

Gnomad4 AMR AF: 0.0370

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.0815

Gnomad4 FIN AF: 0.0363

Gnomad4 NFE AF: 0.0278

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0315 Hom.: 251

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;.;.
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

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: rs17646069; hg19: chr13-42803263; COSMIC: COSV54932494;