Variant 3-142225340-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001039547.3(GK5):c.116C>A(p.Ala39Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,228 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GK5
NM_001039547.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.983

Variant links:

Genes affected

GK5 (HGNC:28635): (glycerol kinase 5) 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. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

GK5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06746253).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GK5	NM_001039547.3 link	c.116C>A	p.Ala39Glu	missense_variant	1/16	ENST00000392993.7	NP_001034636.1	Q6ZS86-1
GK5	XM_047447897.1 link	c.116C>A	p.Ala39Glu	missense_variant	1/13		XP_047303853.1
GK5	NR_033289.2 link	n.246C>A		non_coding_transcript_exon_variant	1/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GK5	ENST00000392993.7 link	c.116C>A	p.Ala39Glu	missense_variant	1/16	1	NM_001039547.3	ENSP00000418001.1		Q6ZS86-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152110

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:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1406160

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

694948

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2024

The c.116C>A (p.A39E) alteration is located in exon 1 (coding exon 1) of the GK5 gene. This alteration results from a C to A substitution at nucleotide position 116, causing the alanine (A) at amino acid position 39 to be replaced by a glutamic acid (E). 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

0.10

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.018

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.64

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.060

PrimateAI

Uncertain

0.75

PROVEAN

Benign

0.11

REVEL

Benign

0.034

Sift

Benign

1.0

Sift4G

Benign

0.96

Polyphen

0.0

Vest4

0.29

MutPred

0.33

Gain of sheet (P = 0.039);

MVP

0.21

MPC

0.64

ClinPred

0.11

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.041

gMVP

0.30

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