rs766772846

Variant names:

• chrX-30669373-G-A
• rs766772846
• NM_001205019.2:c.259+1255G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PP5_Moderate BP4 BS2_Supporting

The NM_001205019.2(GK):​c.259+1255G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000355 in 109,715 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: 𝑓 0.00036 (0 hom., 10 hem., cov: 21)
• Consequence: GK NM_001205019.2 intron
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: -0.705

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 Uncertain_significance. Variant got 0 ACMG points.

• PP5: Variant X-30669373-G-A is Pathogenic according to our data. Variant chrX-30669373-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 1685851.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0). . Strength limited to SUPPORTING due to the PP5.
• BS2: High Hemizygotes in GnomAd4 at 10 XL geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GK	NM_001205019.2	c.259+1255G>A		intron_variant	Intron 3 of 20	ENST00000427190.6	NP_001191948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GK	ENST00000427190.6	c.259+1255G>A		intron_variant	Intron 3 of 20	5	NM_001205019.2	ENSP00000401720.2

Frequencies

GnomAD3 genomes AF: 0.000356 AC: 39 AN: 109670 Hom.: 0 Cov.: 21 AF XY: 0.000313 AC XY: 10 AN XY: 31976

Gnomad AFR AF: 0.00103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000392

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: 0.0000380

Gnomad OTH AF: 0.00137

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

GnomAD4 genome AF: 0.000355 AC: 39 AN: 109715 Hom.: 0 Cov.: 21 AF XY: 0.000312 AC XY: 10 AN XY: 32031

Gnomad4 AFR AF: 0.00103

Gnomad4 AMR AF: 0.000391

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000380

Gnomad4 OTH AF: 0.00136

Alfa AF: 0.000551 Hom.: 3

Bravo AF: 0.000536

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn glycerol kinase deficiency Pathogenic:1

May 04, 2022

Mendelics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	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: rs766772846; hg19: chrX-30687490;