Variant 9-68384494-G-A 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_021965.4(PGM5):c.521G>A(p.Arg174Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000379 in 1,610,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

PGM5
NM_021965.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.87

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:

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=0.042185187).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGM5	NM_021965.4 linkuse as main transcript	c.521G>A	p.Arg174Gln	missense_variant	3/11	ENST00000396396.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGM5	ENST00000396396.6 linkuse as main transcript	c.521G>A	p.Arg174Gln	missense_variant	3/11	2	NM_021965.4	P1	Q15124-1
PGM5	ENST00000396392.5 linkuse as main transcript	c.521G>A	p.Arg174Gln	missense_variant	3/8	1			Q15124-2
PGM5	ENST00000431583.1 linkuse as main transcript	c.323-2969G>A		intron_variant		5
PGM5	ENST00000604870.6 linkuse as main transcript	n.876G>A		non_coding_transcript_exon_variant	6/12	5

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

151886

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000723

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000639

AC:

AN:

250238

Hom.:

AF XY:

0.0000591

AC XY:

AN XY:

135252

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1458416

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

725610

show subpopulations

Gnomad4 AFR exome

AF:

0.000510

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00000541

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.000178

AC:

AN:

152004

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000722

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.000450

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

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

Jan 26, 2022

The c.521G>A (p.R174Q) alteration is located in exon 3 (coding exon 3) of the PGM5 gene. This alteration results from a G to A substitution at nucleotide position 521, causing the arginine (R) at amino acid position 174 to be replaced by a glutamine (Q). 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

0.084

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.45

Cadd

Uncertain

Dann

Uncertain

0.99

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.042

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

N;N

MutationTaster

Benign

0.94

D;D

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.49

N;N

REVEL

Benign

0.13

Sift

Benign

0.28

T;T

Sift4G

Benign

0.31

T;T

Polyphen

0.80

.;P

Vest4

0.22

MVP

0.26

MPC

0.33

ClinPred

0.048

GERP RS

3.5

Varity_R

0.059

gMVP

0.76

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