Variant 9-68384446-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_021965.4(PGM5):c.473C>T(p.Thr158Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,604,748 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000070 ( 1 hom. )

Consequence

PGM5
NM_021965.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.78

Variant links:

Genes affected

PGM5 (HGNC:8908): (phosphoglucomutase 5) Phosphoglucomutases (EC 5.2.2.2.), such as PGM5, are phosphotransferases involved in interconversion of glucose-1-phosphate and glucose-6-phosphate. PGM activity is essential in formation of carbohydrates from glucose-6-phosphate and in formation of glucose-6-phosphate from galactose and glycogen (Edwards et al., 1995 [PubMed 8586438]).[supplied by OMIM, Mar 2008]

PGM5 links:

PGM5 (HGNC:):

PGM5 links:

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/exons	MANE	Protein	UniProt
PGM5	NM_021965.4 linkuse as main transcript	c.473C>T	p.Thr158Met	missense_variant	3/11	ENST00000396396.6	NP_068800.2	Q15124-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PGM5	ENST00000396396.6 linkuse as main transcript	c.473C>T	p.Thr158Met	missense_variant	3/11	2	NM_021965.4	ENSP00000379678.1	Q15124-1
PGM5	ENST00000396392.5 linkuse as main transcript	c.473C>T	p.Thr158Met	missense_variant	3/8	1		ENSP00000379674.1	Q15124-2
PGM5	ENST00000431583.1 linkuse as main transcript	c.323-3017C>T		intron_variant		5		ENSP00000394864.1	Q5JTY7
PGM5	ENST00000604870.6 linkuse as main transcript	n.828C>T		non_coding_transcript_exon_variant	6/12	5

Frequencies

GnomAD3 genomes

AF:

0.000507

AC:

AN:

151896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000985

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000120

AC:

AN:

250164

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

135202

show subpopulations

Gnomad AFR exome

AF:

0.000741

Gnomad AMR exome

AF:

0.0000872

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000985

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000708

Gnomad OTH exome

AF:

0.000657

GnomAD4 exome

AF:

0.0000702

AC:

102

AN:

1452734

Hom.:

Cov.:

AF XY:

0.0000816

AC XY:

AN XY:

723168

show subpopulations

Gnomad4 AFR exome

AF:

0.00118

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000105

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000281

Gnomad4 OTH exome

AF:

0.000250

GnomAD4 genome

AF:

0.000507

AC:

AN:

152014

Hom.:

Cov.:

AF XY:

0.000511

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.00133

Gnomad4 AMR

AF:

0.000984

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.000608

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Aug 13, 2021

The c.473C>T (p.T158M) alteration is located in exon 3 (coding exon 3) of the PGM5 gene. This alteration results from a C to T substitution at nucleotide position 473, causing the threonine (T) at amino acid position 158 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

0.13

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.62

.;D

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

D;D

M_CAP

Uncertain

0.093

MetaRNN

Uncertain

0.44

T;T

MetaSVM

Uncertain

-0.048

MutationAssessor

Pathogenic

2.9

M;M

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-3.4

D;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.011

D;D

Polyphen

0.95

.;P

Vest4

0.82

MVP

0.40

MPC

0.81

ClinPred

0.16

GERP RS

4.7

Varity_R

0.29

gMVP

0.78

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