X-30670451-G-T

Variant names:

• chrX-30670451-G-T
• rs62591597
• NM_001205019.2:c.259+2333G>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.259+2333G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 110,219 control chromosomes in the GnomAD database, including 3,632 homozygotes. There are 9,704 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (3632 hom., 9704 hem., cov: 22)
• Consequence: GK NM_001205019.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.152

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=-0.72).
• BP6: Variant X-30670451-G-T is Benign according to our data. Variant chrX-30670451-G-T is described in ClinVar as [Benign]. Clinvar id is 1295080.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GK	NM_001205019.2	c.259+2333G>T		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+2333G>T		intron_variant	Intron 3 of 20	5	NM_001205019.2	ENSP00000401720.2

Frequencies

GnomAD3 genomes AF: 0.300 AC: 33024 AN: 110169 Hom.: 3631 Cov.: 22 AF XY: 0.299 AC XY: 9689 AN XY: 32447

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.300 AC: 33036 AN: 110219 Hom.: 3632 Cov.: 22 AF XY: 0.299 AC XY: 9704 AN XY: 32507

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.264

Alfa AF: 0.214 Hom.: 1611

Bravo AF: 0.287

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

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	-0.72
CADD	Benign	2.2
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs62591597; hg19: chrX-30688568;