rs619

Positions:

• chrX-30695846-A-G
• chrX-30695846-A-T

Variant summary

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

The NM_001205019.2(GK):​c.553-196A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 111,664 control chromosomes in the GnomAD database, including 3,440 homozygotes. There are 9,683 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (3440 hom., 9683 hem., cov: 24)
• Consequence: GK NM_001205019.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.720

Genes affected

GK (HGNC:4289): (glycerol kinase) The protein encoded by this gene belongs to the FGGY kinase family. This protein is a key enzyme in the regulation of glycerol uptake and metabolism. It catalyzes the phosphorylation of glycerol by ATP, yielding ADP and glycerol-3-phosphate. Mutations in this gene are associated with glycerol kinase deficiency (GKD). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant X-30695846-A-G is Benign according to our data. Variant chrX-30695846-A-G is described in ClinVar as [Benign]. Clinvar id is 1250732.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GK	NM_001205019.2	c.553-196A>G		intron_variant		ENST00000427190.6	NP_001191948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GK	ENST00000427190.6	c.553-196A>G		intron_variant		5	NM_001205019.2	ENSP00000401720	P1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 32146 AN: 111613 Hom.: 3439 Cov.: 24 AF XY: 0.286 AC XY: 9670 AN XY: 33809

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.288 AC: 32152 AN: 111664 Hom.: 3440 Cov.: 24 AF XY: 0.286 AC XY: 9683 AN XY: 33870

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.409

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.259

Alfa AF: 0.322 Hom.: 6807

Bravo AF: 0.275

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

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.78

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: rs619; hg19: chrX-30713963;