7-14583134-T-A

Position:

• chr7-14583134-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001350709.2(DGKB):​c.1437A>T​(p.Leu479Phe) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DGKB NM_001350709.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21

Genes affected

DGKB (HGNC:2850): (diacylglycerol kinase beta) Diacylglycerol kinases (DGKs) are regulators of the intracellular concentration of the second messenger diacylglycerol (DAG) and thus play a key role in cellular processes. Nine mammalian isotypes have been identified, which are encoded by separate genes. Mammalian DGK isozymes contain a conserved catalytic (kinase) domain and a cysteine-rich domain (CRD). The protein encoded by this gene is a diacylglycerol kinase, beta isotype. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2017]

DGKB (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.875

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKB	NM_001350709.2	c.1437A>T	p.Leu479Phe	missense_variant	18/26	ENST00000402815.6	NP_001337638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKB	ENST00000402815.6	c.1437A>T	p.Leu479Phe	missense_variant	18/26	5	NM_001350709.2	ENSP00000384909.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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

May 30, 2024

The c.1440A>T (p.L480F) alteration is located in exon 17 (coding exon 17) of the DGKB gene. This alteration results from a A to T substitution at nucleotide position 1440, causing the leucine (L) at amino acid position 480 to be replaced by a phenylalanine (F). 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	0.78
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T;T;.;.;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.90	D;.;D;D;D
M_CAP	Benign	0.051	D
MetaRNN	Pathogenic	0.87	D;D;D;D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Pathogenic	3.1	M;M;.;.;M
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.5	D;D;D;D;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0030	D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		0.99	D;D;.;.;D
Vest4		0.83
MutPred		0.75		Loss of catalytic residue at L480 (P = 0.0447);Loss of catalytic residue at L480 (P = 0.0447);.;.;Loss of catalytic residue at L480 (P = 0.0447);
MVP		0.62
MPC		0.84
ClinPred		0.98	D
GERP RS		4.2
Varity_R		0.56
gMVP		0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-14622759;