rs9813489

Positions:

• chr3-52292735-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_145262.4(GLYCTK):​c.1181C>T​(p.Thr394Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,608,714 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0090 (20 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (19 hom.)
• Consequence: GLYCTK NM_145262.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.06

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002203524).
• BP6: Variant 3-52292735-C-T is Benign according to our data. Variant chr3-52292735-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 445830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00904 (1377/152346) while in subpopulation AFR AF= 0.0312 (1299/41582). AF 95% confidence interval is 0.0298. There are 20 homozygotes in gnomad4. There are 659 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLYCTK	NM_145262.4	c.1181C>T	p.Thr394Ile	missense_variant	5/5	ENST00000436784.7	NP_660305.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLYCTK	ENST00000436784.7	c.1181C>T	p.Thr394Ile	missense_variant	5/5	1	NM_145262.4	ENSP00000389175.2

Frequencies

GnomAD3 genomes AF: 0.00904 AC: 1376 AN: 152228 Hom.: 20 Cov.: 33

Gnomad AFR AF: 0.0313

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00250 AC: 620 AN: 248344 Hom.: 4 AF XY: 0.00188 AC XY: 253 AN XY: 134332

Gnomad AFR exome AF: 0.0331

Gnomad AMR exome AF: 0.00128

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000331

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000293

Gnomad OTH exome AF: 0.000989

GnomAD4 exome AF: 0.00104 AC: 1515 AN: 1456368 Hom.: 19 Cov.: 32 AF XY: 0.000881 AC XY: 638 AN XY: 723800

Gnomad4 AFR exome AF: 0.0302

Gnomad4 AMR exome AF: 0.00133

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000698

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000279

Gnomad4 OTH exome AF: 0.00205

GnomAD4 genome AF: 0.00904 AC: 1377 AN: 152346 Hom.: 20 Cov.: 33 AF XY: 0.00885 AC XY: 659 AN XY: 74486

Gnomad4 AFR AF: 0.0312

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00185 Hom.: 4

Bravo AF: 0.0103

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0311 AC: 137

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.00299 AC: 363

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000356

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 16, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.1
DANN	Benign	0.77
DEOGEN2	Benign	0.050	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.095
Sift	Benign	0.054	T
Sift4G	Benign	0.20	T
Polyphen		0.0	B
Vest4		0.054
MVP		0.40
MPC		0.11
ClinPred		0.0012	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.043
gMVP		0.49

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

Other links and lift over

dbSNP: rs9813489; hg19: chr3-52326751; COSMIC: COSV99980818; COSMIC: COSV99980818;