rs45540243

Variant names:

• chrX-30667920-A-C
• rs45540243
• NM_001205019.2:c.153-92A>C

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.153-92A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00816 in 553,588 control chromosomes in the GnomAD database, including 140 homozygotes. There are 1,155 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (98 hom., 753 hem., cov: 24)
  • Exomes 𝑓: 0.0036 (42 hom. 402 hem.)
• Consequence: GK NM_001205019.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.339
• 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: XL, AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant X-30667920-A-C is Benign according to our data. Variant chrX-30667920-A-C is described in ClinVar as Benign. ClinVar VariationId is 1286744.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0867 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001205019.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GK	NM_001205019.2	MANE Select	c.153-92A>C		intron	N/A	NP_001191948.1	P32189-3
	GK	NM_001437590.1		c.153-92A>C		intron	N/A	NP_001424519.1	A0A8I5KXY7
	GK	NM_001128127.3		c.153-92A>C		intron	N/A	NP_001121599.1	P32189-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GK	ENST00000427190.6	TSL:5 MANE Select	c.153-92A>C		intron	N/A	ENSP00000401720.2	P32189-3
	GK	ENST00000378943.7	TSL:1	c.153-92A>C		intron	N/A	ENSP00000368226.3	P32189-2
	GK	ENST00000378946.7	TSL:1	c.153-92A>C		intron	N/A	ENSP00000368229.3	P32189-4

Frequencies

GnomAD3 genomes AF: 0.0260 AC: 2911 AN: 112047 Hom.: 99 Cov.: 24

Gnomad AFR AF: 0.0896

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00942

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: 0.000620

Gnomad OTH AF: 0.0153

GnomAD4 exome AF: 0.00364 AC: 1607 AN: 441491 Hom.: 42 AF XY: 0.00263 AC XY: 402 AN XY: 152931

African (AFR) AF: 0.0882 AC: 1152 AN: 13061

American (AMR) AF: 0.00567 AC: 162 AN: 28592

Ashkenazi Jewish (ASJ) AF: 0.0000681 AC: 1 AN: 14677

East Asian (EAS) AF: 0.00 AC: 0 AN: 25075

South Asian (SAS) AF: 0.000389 AC: 15 AN: 38591

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37792

Middle Eastern (MID) AF: 0.00340 AC: 6 AN: 1763

European-Non Finnish (NFE) AF: 0.000326 AC: 84 AN: 258055

Other (OTH) AF: 0.00783 AC: 187 AN: 23885

GnomAD4 genome AF: 0.0260 AC: 2912 AN: 112097 Hom.: 98 Cov.: 24 AF XY: 0.0219 AC XY: 753 AN XY: 34317

African (AFR) AF: 0.0895 AC: 2758 AN: 30831

American (AMR) AF: 0.00932 AC: 98 AN: 10520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3618

South Asian (SAS) AF: 0.00 AC: 0 AN: 2766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.000620 AC: 33 AN: 53202

Other (OTH) AF: 0.0151 AC: 23 AN: 1525

Alfa AF: 0.0559 Hom.: 396

Bravo AF: 0.0304

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.41
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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: rs45540243; hg19: chrX-30686037; COSMIC: COSV66734696; COSMIC: COSV66734696;