X-30668056-A-C

Variant names:

• chrX-30668056-A-C
• NM_001205019.2:c.197A>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001205019.2(GK):​c.197A>C​(p.Glu66Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000976 in 1,024,505 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.8e-7 (0 hom. 0 hem.)
• Consequence: GK NM_001205019.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.87

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GK	NM_001205019.2	c.197A>C	p.Glu66Ala	missense_variant	Exon 3 of 21	ENST00000427190.6	NP_001191948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GK	ENST00000427190.6	c.197A>C	p.Glu66Ala	missense_variant	Exon 3 of 21	5	NM_001205019.2	ENSP00000401720.2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 9.76e-7 AC: 1 AN: 1024505 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 311063

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000129

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn glycerol kinase deficiency Uncertain:1

Aug 06, 2021

New York Genome Center

Significance: Uncertain significance

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
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	.;.;T;.;.
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D;D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.55	D;D;D;D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.5	L;L;L;L;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.6	D;D;.;D;D
REVEL	Uncertain	0.36
Sift	Benign	0.14	T;T;.;T;T
Sift4G	Benign	0.38	T;T;T;T;T
Polyphen		0.28, 0.17	.;B;.;B;.
Vest4		0.55
MutPred		0.49		Loss of ubiquitination at K70 (P = 0.198);Loss of ubiquitination at K70 (P = 0.198);Loss of ubiquitination at K70 (P = 0.198);Loss of ubiquitination at K70 (P = 0.198);Loss of ubiquitination at K70 (P = 0.198);
MVP		0.58
MPC		1.2
ClinPred		0.90	D
GERP RS		5.6
Varity_R		0.73
gMVP		0.79

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-30686173;