7-14698108-G-C

Variant names:

• chr7-14698108-G-C
• NM_001350709.2:c.578C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001350709.2(DGKB):​c.578C>G​(p.Thr193Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 9.93

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKB	NM_001350709.2	c.578C>G	p.Thr193Ser	missense_variant	Exon 8 of 26	ENST00000402815.6	NP_001337638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKB	ENST00000402815.6	c.578C>G	p.Thr193Ser	missense_variant	Exon 8 of 26	5	NM_001350709.2	ENSP00000384909.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.578C>G (p.T193S) alteration is located in exon 7 (coding exon 7) of the DGKB gene. This alteration results from a C to G substitution at nucleotide position 578, causing the threonine (T) at amino acid position 193 to be replaced by a serine (S). 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	Benign	0.14
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;T;.;.;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;.;D;D;D
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.53	D;D;D;D;D
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.58	N;N;.;.;N
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.8	N;N;N;N;N
REVEL	Uncertain	0.32
Sift	Benign	0.61	T;T;T;T;T
Sift4G	Benign	0.50	T;T;T;T;T
Polyphen		1.0	D;D;.;.;B
Vest4		0.63
MutPred		0.49		Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);.;Gain of relative solvent accessibility (P = 0.09);
MVP		0.85
MPC		0.74
ClinPred		0.97	D
GERP RS		5.3
Varity_R		0.26
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr7-14737733;