dbSNP rs373968401: DGKG:p.Pro551Ser (chr3-186251869-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001346.3(DGKG):c.1651C>T(p.Pro551Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,609,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P551R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

DGKG
NM_001346.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.17

Publications

2 publications found

Variant links:

Genes affected

DGKG (HGNC:2853): (diacylglycerol kinase gamma) This gene encodes an enzyme that is a member of the type I subfamily of diacylglycerol kinases, which are involved in lipid metabolism. These enzymes generate phosphatidic acid by catalyzing the phosphorylation of diacylglycerol, a fundamental lipid second messenger that activates numerous proteins, including protein kinase C isoforms, Ras guanyl nucleotide-releasing proteins and some transient receptor potential channels. Diacylglycerol kinase gamma has been implicated in cell cycle regulation and in the negative regulation of macrophage differentiation in leukemia cells. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

DGKG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.061662257).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DGKG	NM_001346.3	MANE Select	c.1651C>T	p.Pro551Ser	missense	Exon 19 of 25	NP_001337.2	P49619-1
DGKG	NM_001080744.2		c.1576C>T	p.Pro526Ser	missense	Exon 18 of 24	NP_001074213.1	P49619-2
DGKG	NM_001080745.2		c.1534C>T	p.Pro512Ser	missense	Exon 18 of 24	NP_001074214.1	P49619-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DGKG	ENST00000265022.8	TSL:1 MANE Select	c.1651C>T	p.Pro551Ser	missense	Exon 19 of 25	ENSP00000265022.3	P49619-1
DGKG	ENST00000344484.8	TSL:1	c.1576C>T	p.Pro526Ser	missense	Exon 18 of 24	ENSP00000339777.4	P49619-2
DGKG	ENST00000480809.5	TSL:1	n.1914C>T		non_coding_transcript_exon	Exon 18 of 24

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000404

AC:

AN:

247762

AF XY:

0.0000299

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000894

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000220

AC:

AN:

1457428

Hom.:

Cov.:

AF XY:

0.0000262

AC XY:

AN XY:

724826

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33296

American (AMR)

AF:

0.00

AC:

AN:

44244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25834

East Asian (EAS)

AF:

0.00

AC:

AN:

39550

South Asian (SAS)

AF:

0.00

AC:

AN:

85788

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.0000270

AC:

AN:

1109490

Other (OTH)

AF:

0.0000332

AC:

AN:

60198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000284

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.21

DEOGEN2

Benign

0.074

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.26

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0052

MetaRNN

Benign

0.062

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.4

PhyloP100

2.2

PrimateAI

Benign

0.47

PROVEAN

Benign

1.5

REVEL

Benign

0.12

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0090

Vest4

0.26

MVP

0.45

MPC

0.12

ClinPred

0.092

GERP RS

4.1

Varity_R

0.053

gMVP

0.35

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over