X-50391446-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001013742.4(DGKK):c.1835T>A(p.Ile612Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00333 in 1,209,523 control chromosomes in the GnomAD database, including 96 homozygotes. There are 1,079 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (49 hom., 541 hem., cov: 23)
  • Exomes 𝑓: 0.0019 (47 hom. 538 hem.)
• Consequence: DGKK NM_001013742.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.17

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0054518282).
• BP6: Variant X-50391446-A-T is Benign according to our data. Variant chrX-50391446-A-T is described in ClinVar as [Benign]. Clinvar id is 785700.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGKK	NM_001013742.4	c.1835T>A	p.Ile612Asn	missense_variant	11/28	ENST00000611977.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGKK	ENST00000611977.2	c.1835T>A	p.Ile612Asn	missense_variant	11/28	1	NM_001013742.4	P1

Frequencies

GnomAD3 genomes AF: 0.0179 AC: 2001 AN: 111939 Hom.: 49 Cov.: 23 AF XY: 0.0159 AC XY: 544 AN XY: 34117

Gnomad AFR AF: 0.0624

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00587

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000373

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000150

Gnomad OTH AF: 0.00989

GnomAD3 exomes AF: 0.00474 AC: 857 AN: 180875 Hom.: 21 AF XY: 0.00342 AC XY: 229 AN XY: 66965

Gnomad AFR exome AF: 0.0608

Gnomad AMR exome AF: 0.00300

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000526

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000148

Gnomad OTH exome AF: 0.00202

GnomAD4 exome AF: 0.00185 AC: 2034 AN: 1097530 Hom.: 47 Cov.: 30 AF XY: 0.00148 AC XY: 538 AN XY: 363168

Gnomad4 AFR exome AF: 0.0631

Gnomad4 AMR exome AF: 0.00307

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000924

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000416

Gnomad4 OTH exome AF: 0.00443

GnomAD4 genome AF: 0.0178 AC: 1998 AN: 111993 Hom.: 49 Cov.: 23 AF XY: 0.0158 AC XY: 541 AN XY: 34181

Gnomad4 AFR AF: 0.0622

Gnomad4 AMR AF: 0.00576

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000374

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000150

Gnomad4 OTH AF: 0.00977

Alfa AF: 0.00374 Hom.: 81

Bravo AF: 0.0210

ESP6500AA AF: 0.0554 AC: 196

ESP6500EA AF: 0.000153 AC: 1

ExAC AF: 0.00520 AC: 629

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 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	18
Dann	Benign	0.67
DEOGEN2	Benign	0.10	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.0055	T
PrimateAI	Uncertain	0.60	T
Sift4G	Uncertain	0.0040	D
Polyphen		0.86	P
Vest4		0.20
MVP		0.18
GERP RS		-0.052
Varity_R		0.17
gMVP		0.90

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: rs138086016; hg19: chrX-50134444;