rs778881211

Variant names:

• chr4-79406697-T-A
• NM_033214.3:c.1504A>T

Your query was ambiguous. Multiple possible variants found:

• chr4-79406697-T-A
• chr4-79406697-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033214.3(GK2):​c.1504A>T​(p.Thr502Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. T502A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: GK2 NM_033214.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.73

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26063722).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GK2	NM_033214.3	c.1504A>T	p.Thr502Ser	missense_variant	Exon 1 of 1	ENST00000358842.5	NP_149991.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GK2	ENST00000358842.5	c.1504A>T	p.Thr502Ser	missense_variant	Exon 1 of 1	6	NM_033214.3	ENSP00000351706.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461882 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727242

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: 0.00000809

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.073
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.19
Sift	Benign	0.46	T
Sift4G	Benign	0.48	T
Polyphen		0.14	B
Vest4		0.24
MutPred		0.42		Gain of glycosylation at T502 (P = 0.0088);
MVP		0.86
MPC		0.079
ClinPred		0.41	T
GERP RS		3.9
Varity_R		0.061
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-80327851;