Variant 3-52290413-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_145262.4(GLYCTK):c.71C>T(p.Ser24Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,610,182 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 2 hom. )

Consequence

GLYCTK
NM_145262.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.482

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006262362).

BP6

Variant 3-52290413-C-T is Benign according to our data. Variant chr3-52290413-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1590817.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000146 (213/1457820) while in subpopulation SAS AF= 0.00234 (202/86234). AF 95% confidence interval is 0.00208. There are 2 homozygotes in gnomad4_exome. There are 160 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLYCTK	NM_145262.4 linkuse as main transcript	c.71C>T	p.Ser24Leu	missense_variant	2/5	ENST00000436784.7	NP_660305.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLYCTK	ENST00000436784.7 linkuse as main transcript	c.71C>T	p.Ser24Leu	missense_variant	2/5	1	NM_145262.4	ENSP00000389175	P1	Q8IVS8-1
GLYCTK-AS1	ENST00000493616.1 linkuse as main transcript	n.304-1689G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000336

AC:

AN:

243998

Hom.:

AF XY:

0.000456

AC XY:

AN XY:

133644

show subpopulations

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 SAS exome

AF:

0.00255

Gnomad FIN exome

AF:

0.0000511

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000498

GnomAD4 exome

AF:

0.000146

AC:

213

AN:

1457820

Hom.:

Cov.:

AF XY:

0.000221

AC XY:

160

AN XY:

725432

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00234

Gnomad4 FIN exome

AF:

0.0000201

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152362

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.000347

AC:

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.038

.;.;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.68

T;T;T;.

M_CAP

Benign

0.012

MetaRNN

Benign

0.0063

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.68

N;N;N;N

REVEL

Benign

0.010

Sift

Benign

0.039

D;T;D;T

Sift4G

Benign

0.13

T;T;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.10

MutPred

0.34

Loss of phosphorylation at S24 (P = 0.0196);Loss of phosphorylation at S24 (P = 0.0196);Loss of phosphorylation at S24 (P = 0.0196);Loss of phosphorylation at S24 (P = 0.0196);

MVP

0.28

MPC

0.090

ClinPred

0.019

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.057

gMVP

0.54

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over