chrX-50400967-G-A

Variant names:

• chrX-50400967-G-A
• rs1934190
• NM_001013742.4:c.1411+70C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001013742.4(DGKK):​c.1411+70C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000909 in 110,028 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000091 (0 hom., 1 hem., cov: 22)
• Consequence: DGKK NM_001013742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.971
• Publications: 7 publications found

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

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 (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGKK	NM_001013742.4	c.1411+70C>T		intron_variant	Intron 8 of 27	ENST00000611977.2	NP_001013764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGKK	ENST00000611977.2	c.1411+70C>T		intron_variant	Intron 8 of 27	1	NM_001013742.4	ENSP00000477515.1

Frequencies

GnomAD3 genomes AF: 0.00000909 AC: 1 AN: 109974 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000331

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: 0.00

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00000909 AC: 1 AN: 110028 Hom.: 0 Cov.: 22 AF XY: 0.0000310 AC XY: 1 AN XY: 32284

African (AFR) AF: 0.0000331 AC: 1 AN: 30235

American (AMR) AF: 0.00 AC: 0 AN: 10291

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2624

East Asian (EAS) AF: 0.00 AC: 0 AN: 3434

South Asian (SAS) AF: 0.00 AC: 0 AN: 2516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5809

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 213

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52741

Other (OTH) AF: 0.00 AC: 0 AN: 1490

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.93
PhyloP100		-0.97

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

Other links and lift over

dbSNP: rs1934190; hg19: chrX-50143965;