4-79407450-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033214.3(GK2):​c.751G>A​(p.Val251Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GK2
NM_033214.3 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.506
Variant links:
Genes affected
GK2 (HGNC:4291): (glycerol kinase 2) Predicted to enable glycerol kinase activity. Predicted to be involved in several processes, including glycerol metabolic process; glycerol-3-phosphate biosynthetic process; and triglyceride metabolic process. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GK2NM_033214.3 linkc.751G>A p.Val251Met missense_variant Exon 1 of 1 ENST00000358842.5 NP_149991.2 Q14410A0A140VKG0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GK2ENST00000358842.5 linkc.751G>A p.Val251Met missense_variant Exon 1 of 1 6 NM_033214.3 ENSP00000351706.3 Q14410

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461872
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 05, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.751G>A (p.V251M) alteration is located in exon 1 (coding exon 1) of the GK2 gene. This alteration results from a G to A substitution at nucleotide position 751, causing the valine (V) at amino acid position 251 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Benign
-0.049
T
BayesDel_noAF
Benign
-0.31
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.060
T
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Benign
0.72
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.026
D
MetaRNN
Uncertain
0.48
T
MetaSVM
Benign
-0.49
T
MutationAssessor
Pathogenic
3.3
M
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-2.2
N
REVEL
Uncertain
0.36
Sift
Benign
0.092
T
Sift4G
Uncertain
0.034
D
Polyphen
0.98
D
Vest4
0.50
MutPred
0.64
Loss of catalytic residue at V251 (P = 0.0054);
MVP
0.62
MPC
0.38
ClinPred
0.97
D
GERP RS
3.1
Varity_R
0.086
gMVP
0.67

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.21
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.21
Position offset: 3

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-80328604; API