Genetic Variant GK:p.Ser83Phe (chrX-30668107-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001205019.2(GK):c.248C>T(p.Ser83Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000114 in 873,641 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000011 ( 0 hom. 1 hem. )

Consequence

GK
NM_001205019.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.51

Publications

0 publications found

Variant links:

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

GK links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41140664).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GK	NM_001205019.2	MANE Select	c.248C>T	p.Ser83Phe	missense	Exon 3 of 21	NP_001191948.1	P32189-3
GK	NM_001437590.1		c.248C>T	p.Ser83Phe	missense	Exon 3 of 21	NP_001424519.1	A0A8I5KXY7
GK	NM_001128127.3		c.248C>T	p.Ser83Phe	missense	Exon 3 of 20	NP_001121599.1	P32189-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GK	ENST00000427190.6	TSL:5 MANE Select	c.248C>T	p.Ser83Phe	missense	Exon 3 of 21	ENSP00000401720.2	P32189-3
GK	ENST00000378943.7	TSL:1	c.248C>T	p.Ser83Phe	missense	Exon 3 of 20	ENSP00000368226.3	P32189-2
GK	ENST00000378946.7	TSL:1	c.248C>T	p.Ser83Phe	missense	Exon 3 of 20	ENSP00000368229.3	P32189-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000548

AC:

AN:

182494

AF XY:

0.0000149

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000114

AC:

AN:

873641

Hom.:

Cov.:

AF XY:

0.00000408

AC XY:

AN XY:

244923

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22313

American (AMR)

AF:

0.0000286

AC:

AN:

34912

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17979

East Asian (EAS)

AF:

0.00

AC:

AN:

29225

South Asian (SAS)

AF:

0.00

AC:

AN:

49561

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40445

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3652

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

636848

Other (OTH)

AF:

0.00

AC:

AN:

38706

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.98

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.51

MutationAssessor

Pathogenic

3.0

PhyloP100

7.5

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.29

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.0090

Polyphen

0.53

Vest4

0.35

MutPred

0.67

Loss of catalytic residue at S83 (P = 0.0519)

MVP

0.59

MPC

1.8

ClinPred

0.87

GERP RS

4.7

Varity_R

0.61

gMVP

0.69

Mutation Taster

=67/33

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over