X-30670598-ATT-AT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001205019.2(GK):​c.259+2491delT 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 0.023 (50 hom., 608 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.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0679 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0226 AC: 2402 AN: 106096 Hom.: 49 Cov.: 16

Gnomad AFR AF: 0.0702

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0106

Gnomad ASJ AF: 0.0253

Gnomad EAS AF: 0.00148

Gnomad SAS AF: 0.00520

Gnomad FIN AF: 0.00162

Gnomad MID AF: 0.0228

Gnomad NFE AF: 0.00224

Gnomad OTH AF: 0.0238

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

GnomAD4 genome AF: 0.0227 AC: 2411 AN: 106116 Hom.: 50 Cov.: 16 AF XY: 0.0203 AC XY: 608 AN XY: 29910

African (AFR) AF: 0.0704 AC: 2063 AN: 29308

American (AMR) AF: 0.0106 AC: 105 AN: 9892

Ashkenazi Jewish (ASJ) AF: 0.0253 AC: 65 AN: 2567

East Asian (EAS) AF: 0.00148 AC: 5 AN: 3377

South Asian (SAS) AF: 0.00563 AC: 14 AN: 2486

European-Finnish (FIN) AF: 0.00162 AC: 8 AN: 4934

Middle Eastern (MID) AF: 0.0201 AC: 4 AN: 199

European-Non Finnish (NFE) AF: 0.00222 AC: 114 AN: 51296

Other (OTH) AF: 0.0235 AC: 33 AN: 1402

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 (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: rs34172820; hg19: chrX-30688715;