dbSNP rs1246343210: GK:p.Ser83Tyr (chrX-30668107-C-A) – 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>A(p.Ser83Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S83F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

GK
NM_001205019.2 missense

Scores

Clinical Significance

Not reported in ClinVar

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=0.34244555).

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>A	p.Ser83Tyr	missense	Exon 3 of 21	NP_001191948.1	P32189-3
GK	NM_001437590.1		c.248C>A	p.Ser83Tyr	missense	Exon 3 of 21	NP_001424519.1	A0A8I5KXY7
GK	NM_001128127.3		c.248C>A	p.Ser83Tyr	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>A	p.Ser83Tyr	missense	Exon 3 of 21	ENSP00000401720.2	P32189-3
GK	ENST00000378943.7	TSL:1	c.248C>A	p.Ser83Tyr	missense	Exon 3 of 20	ENSP00000368226.3	P32189-2
GK	ENST00000378946.7	TSL:1	c.248C>A	p.Ser83Tyr	missense	Exon 3 of 20	ENSP00000368229.3	P32189-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

873634

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

244916

African (AFR)

AF:

0.00

AC:

AN:

22313

American (AMR)

AF:

0.00

AC:

AN:

34912

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17978

East Asian (EAS)

AF:

0.00

AC:

AN:

29225

South Asian (SAS)

AF:

0.00

AC:

AN:

49560

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:

636843

Other (OTH)

AF:

0.00

AC:

AN:

38706

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.3

PhyloP100

7.5

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.27

Sift

Uncertain

0.0050

Sift4G

Benign

0.061

Polyphen

0.70

Vest4

0.34

MutPred

0.59

Gain of catalytic residue at L78 (P = 0.0884)

MVP

0.50

MPC

1.9

ClinPred

0.96

GERP RS

4.7

Varity_R

0.60

gMVP

0.73

Mutation Taster

=71/29

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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