12-55938971-T-A

Position:

• chr12-55938971-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001345.5(DGKA):​c.456T>A​(p.Asp152Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: DGKA NM_001345.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.195

Genes affected

DGKA (HGNC:2849): (diacylglycerol kinase alpha) The protein encoded by this gene belongs to the eukaryotic diacylglycerol kinase family. It acts as a modulator that competes with protein kinase C for the second messenger diacylglycerol in intracellular signaling pathways. It also plays an important role in the resynthesis of phosphatidylinositols and phosphorylating diacylglycerol to phosphatidic acid. Several transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Apr 2017]

DGKA (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41980898).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKA	NM_001345.5	c.456T>A	p.Asp152Glu	missense_variant	7/24	ENST00000331886.10	NP_001336.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKA	ENST00000331886.10	c.456T>A	p.Asp152Glu	missense_variant	7/24	5	NM_001345.5	ENSP00000328405.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2024

The c.456T>A (p.D152E) alteration is located in exon 7 (coding exon 6) of the DGKA gene. This alteration results from a T to A substitution at nucleotide position 456, causing the aspartic acid (D) at amino acid position 152 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T;.;T;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.47	N
LIST_S2	Uncertain	0.88	.;D;D;.
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.42	T;T;T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.5	L;.;L;L
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.7	D;D;D;D
REVEL	Benign	0.12
Sift	Uncertain	0.021	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.97	D;D;D;D
Vest4		0.28
MutPred		0.39		Gain of catalytic residue at L149 (P = 8e-04);.;Gain of catalytic residue at L149 (P = 8e-04);Gain of catalytic residue at L149 (P = 8e-04);
MVP		0.78
MPC		0.55
ClinPred		0.86	D
GERP RS		-0.22
Varity_R		0.58
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1015027274; hg19: chr12-56332755;