X-30670451-G-T

Variant names:

• chrX-30670451-G-T
• rs62591597
• NM_001205019.2:c.259+2333G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

GK Gene-Disease associations (from GenCC):

• inborn glycerol kinase deficiency

  Inheritance: AR, XL Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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

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

African (AFR) AF: 0.235 AC: 7139 AN: 30358

American (AMR) AF: 0.295 AC: 3039 AN: 10296

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 718 AN: 2629

East Asian (EAS) AF: 0.410 AC: 1422 AN: 3468

South Asian (SAS) AF: 0.420 AC: 1105 AN: 2629

European-Finnish (FIN) AF: 0.411 AC: 2335 AN: 5688

Middle Eastern (MID) AF: 0.236 AC: 51 AN: 216

European-Non Finnish (NFE) AF: 0.317 AC: 16736 AN: 52773

Other (OTH) AF: 0.264 AC: 396 AN: 1499

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.2
DANN	Benign	0.84
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs62591597; hg19: chrX-30688568;