4-961569-C-T

Variant names:

• chr4-961569-C-T
• rs138148951
• NM_001347.4:c.2472G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001347.4(DGKQ):​c.2472G>A​(p.Ser824Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00071 in 1,608,786 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00059 (4 hom.)
• Consequence: DGKQ NM_001347.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.00
• Publications: 1 publications found

Genes affected

DGKQ (HGNC:2856): (diacylglycerol kinase theta) The protein encoded by this gene contains three cysteine-rich domains, a proline-rich region, and a pleckstrin homology domain with an overlapping Ras-associating domain. It is localized in the speckle domains of the nucleus, and mediates the regeneration of phosphatidylinositol (PI) from diacylglycerol in the PI-cycle during cell signal transduction. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.064).
• BP6: Variant 4-961569-C-T is Benign according to our data. Variant chr4-961569-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3257705.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKQ	NM_001347.4	MANE Select	c.2472G>A	p.Ser824Ser	synonymous	Exon 21 of 23	NP_001338.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGKQ	ENST00000273814.8	TSL:1 MANE Select	c.2472G>A	p.Ser824Ser	synonymous	Exon 21 of 23	ENSP00000273814.3	P52824
	DGKQ	ENST00000932945.1		c.2559G>A	p.Ser853Ser	synonymous	Exon 21 of 23	ENSP00000603004.1
	DGKQ	ENST00000970135.1		c.2514G>A	p.Ser838Ser	synonymous	Exon 21 of 23	ENSP00000640194.1

Frequencies

GnomAD3 genomes AF: 0.00187 AC: 284 AN: 152200 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00432

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00102 AC: 238 AN: 232848 AF XY: 0.000971

Gnomad AFR exome AF: 0.00456

Gnomad AMR exome AF: 0.00169

Gnomad ASJ exome AF: 0.00126

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000500

Gnomad NFE exome AF: 0.000753

Gnomad OTH exome AF: 0.00281

GnomAD4 exome AF: 0.000589 AC: 858 AN: 1456468 Hom.: 4 Cov.: 34 AF XY: 0.000625 AC XY: 453 AN XY: 724462

African (AFR) AF: 0.00425 AC: 142 AN: 33378

American (AMR) AF: 0.00199 AC: 88 AN: 44310

Ashkenazi Jewish (ASJ) AF: 0.000692 AC: 18 AN: 25996

East Asian (EAS) AF: 0.00 AC: 0 AN: 39494

South Asian (SAS) AF: 0.000547 AC: 47 AN: 85866

European-Finnish (FIN) AF: 0.0000195 AC: 1 AN: 51236

Middle Eastern (MID) AF: 0.00300 AC: 17 AN: 5666

European-Non Finnish (NFE) AF: 0.000409 AC: 454 AN: 1110432

Other (OTH) AF: 0.00151 AC: 91 AN: 60090

GnomAD4 genome AF: 0.00186 AC: 284 AN: 152318 Hom.: 1 Cov.: 33 AF XY: 0.00183 AC XY: 136 AN XY: 74482

African (AFR) AF: 0.00431 AC: 179 AN: 41566

American (AMR) AF: 0.00431 AC: 66 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68020

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00143 Hom.: 1

Bravo AF: 0.00274

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.24
DANN	Benign	0.89
PhyloP100		-4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs138148951; hg19: chr4-955357; COSMIC: COSV99298290; COSMIC: COSV99298290;