rs12535157

Positions:

• chr7-137422201-C-A
• chr7-137422201-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321708.2(DGKI):​c.2762-9994G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,028 control chromosomes in the GnomAD database, including 8,240 homozygotes. 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 0.30 (8240 hom., cov: 32)
• Consequence: DGKI NM_001321708.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.266

Genes affected

DGKI (HGNC:2855): (diacylglycerol kinase iota) This gene is a member of the type IV diacylglycerol kinase subfamily. Diacylglycerol kinases regulate the intracellular concentration of diacylglycerol through its phosphorylation, producing phosphatidic acid. The specific role of the enzyme encoded by this gene is undetermined, however, it may play a crucial role in the production of phosphatidic acid in the retina or in recessive forms of retinal degeneration. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGKI	NM_001321708.2	c.2762-9994G>T		intron_variant		ENST00000614521.2	NP_001308637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGKI	ENST00000614521.2	c.2762-9994G>T		intron_variant		5	NM_001321708.2	ENSP00000479053	P3

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45781 AN: 151910 Hom.: 8232 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.301 AC: 45801 AN: 152028 Hom.: 8240 Cov.: 32 AF XY: 0.309 AC XY: 22986 AN XY: 74316

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.649

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.335

Gnomad4 OTH AF: 0.326

Alfa AF: 0.320 Hom.: 1740

Bravo AF: 0.305

Asia WGS AF: 0.538 AC: 1874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.7
DANN	Benign	0.72

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: rs12535157; hg19: chr7-137106947;