X-50371729-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001013742.4(DGKK):c.3607C>T(p.Pro1203Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,189,586 control chromosomes in the GnomAD database, including 3 homozygotes. There are 492 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., 58 hem., cov: 22)
  • Exomes 𝑓: 0.0012 (3 hom. 434 hem.)
• Consequence: DGKK NM_001013742.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.218

Genes affected

DGKK (HGNC:32395): (diacylglycerol kinase kappa) The protein encoded by this gene is an enzyme that phosphorylates diacylglycerol, converting it to phosphatidic acid. The encoded protein is a membrane protein and is inhibited by hydrogen peroxide. Variations in this gene have been associated with hypospadias. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0070827007).
• BP6: Variant X-50371729-G-A is Benign according to our data. Variant chrX-50371729-G-A is described in ClinVar as [Benign]. Clinvar id is 734433.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd at 58 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGKK	NM_001013742.4	c.3607C>T	p.Pro1203Ser	missense_variant	26/28	ENST00000611977.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKK	ENST00000611977.2	c.3607C>T	p.Pro1203Ser	missense_variant	26/28	1	NM_001013742.4	P1

Frequencies

GnomAD3 genomes AF: 0.00136 AC: 152 AN: 111507 Hom.: 0 Cov.: 22 AF XY: 0.00172 AC XY: 58 AN XY: 33725

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: 0.000762

Gnomad FIN AF: 0.0151

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00111

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00214 AC: 357 AN: 166706 Hom.: 0 AF XY: 0.00204 AC XY: 112 AN XY: 54776

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000345

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00174

Gnomad FIN exome AF: 0.0154

Gnomad NFE exome AF: 0.00113

Gnomad OTH exome AF: 0.00120

GnomAD4 exome AF: 0.00122 AC: 1311 AN: 1078024 Hom.: 3 Cov.: 26 AF XY: 0.00125 AC XY: 434 AN XY: 346112

Gnomad4 AFR exome AF: 0.000115

Gnomad4 AMR exome AF: 0.000346

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00173

Gnomad4 FIN exome AF: 0.0157

Gnomad4 NFE exome AF: 0.000646

Gnomad4 OTH exome AF: 0.000904

GnomAD4 genome AF: 0.00136 AC: 152 AN: 111562 Hom.: 0 Cov.: 22 AF XY: 0.00172 AC XY: 58 AN XY: 33790

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000764

Gnomad4 FIN AF: 0.0151

Gnomad4 NFE AF: 0.00111

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00118 Hom.: 9

Bravo AF: 0.000434

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000304 AC: 1

ESP6500EA AF: 0.000155 AC: 1

ExAC AF: 0.00201 AC: 242

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 18, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	11
Dann	Benign	0.62
DEOGEN2	Benign	0.032	T
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0071	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.30	T
Sift4G	Benign	0.17	T
Polyphen		1.0	D
Vest4		0.088
MVP		0.092
GERP RS		3.1
Varity_R		0.057
gMVP		0.11

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

LitVar

Other links and lift over

dbSNP: rs192915815; hg19: chrX-50114728;