X-30670598-A-AT

Variant names:

• chrX-30670598-A-AT
• rs34172820
• NM_001205019.2:c.259+2491dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001205019.2(GK):​c.259+2491dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00077 (2 hom., 22 hem., cov: 16)
• Consequence: GK NM_001205019.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149
• 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000772 (82/106240) while in subpopulation SAS AF = 0.0149 (37/2487). AF 95% confidence interval is 0.0111. There are 2 homozygotes in GnomAd4. There are 22 alleles in the male GnomAd4 subpopulation. Median coverage is 16. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR,XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GK	NM_001205019.2	c.259+2491dupT		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+2480_259+2481insT		intron_variant	Intron 3 of 20	5	NM_001205019.2	ENSP00000401720.2

Frequencies

GnomAD3 genomes AF: 0.000772 AC: 82 AN: 106220 Hom.: 2 Cov.: 16

Gnomad AFR AF: 0.00140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000202

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000295

Gnomad SAS AF: 0.0148

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000195

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000772 AC: 82 AN: 106240 Hom.: 2 Cov.: 16 AF XY: 0.000734 AC XY: 22 AN XY: 29958

African (AFR) AF: 0.00140 AC: 41 AN: 29331

American (AMR) AF: 0.000202 AC: 2 AN: 9903

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2570

East Asian (EAS) AF: 0.000296 AC: 1 AN: 3381

South Asian (SAS) AF: 0.0149 AC: 37 AN: 2487

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4967

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 199

European-Non Finnish (NFE) AF: 0.0000195 AC: 1 AN: 51342

Other (OTH) AF: 0.00 AC: 0 AN: 1405

Alfa AF: 0.000157 Hom.: 297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs34172820; hg19: chrX-30688715;