Genetic Variant NM_145262.4:c.169C>T (chr3-52290511-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_145262.4(GLYCTK):c.169C>T(p.Arg57Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,158 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

GLYCTK
NM_145262.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.41

Publications

0 publications found

Variant links:

Genes affected

GLYCTK (HGNC:24247): (glycerate kinase) This locus encodes a member of the glycerate kinase type-2 family. The encoded enzyme catalyzes the phosphorylation of (R)-glycerate and may be involved in serine degradation and fructose metabolism. Decreased activity of the encoded enzyme may be associated with the disease D-glyceric aciduria. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2009]

GLYCTK links:

GLYCTK-AS1 (HGNC:41043): (GLYCTK antisense RNA 1)

GLYCTK-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145262.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLYCTK	NM_145262.4	MANE Select	c.169C>T	p.Arg57Trp	missense	Exon 2 of 5	NP_660305.2
GLYCTK	NM_001437621.1		c.169C>T	p.Arg57Trp	missense	Exon 1 of 4	NP_001424550.1
GLYCTK	NM_001144951.2		c.169C>T	p.Arg57Trp	missense	Exon 2 of 4	NP_001138423.1	Q8IVS8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLYCTK	ENST00000436784.7	TSL:1 MANE Select	c.169C>T	p.Arg57Trp	missense	Exon 2 of 5	ENSP00000389175.2	Q8IVS8-1
GLYCTK	ENST00000477382.2	TSL:1	c.169C>T	p.Arg57Trp	missense	Exon 2 of 4	ENSP00000419008.1
GLYCTK	ENST00000473032.5	TSL:1	c.169C>T	p.Arg57Trp	missense	Exon 2 of 5	ENSP00000418951.1	Q8IVS8-7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

250318

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000753

AC:

AN:

1461158

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726900

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52720

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000719

AC:

AN:

1112000

Other (OTH)

AF:

0.00

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.066

MetaRNN

Uncertain

0.66

MetaSVM

Benign

-0.68

MutationAssessor

Pathogenic

3.5

PhyloP100

2.4

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-5.1

REVEL

Benign

0.20

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.66

MutPred

0.46

Loss of disorder (P = 0.0077)

MVP

0.80

MPC

0.51

ClinPred

0.99

GERP RS

3.5

PromoterAI

-0.0080

Neutral

(source)

Varity_R

0.77

gMVP

0.63

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over