Genetic Variant NM_021965.4:c.49G>A (chr9-68357176-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021965.4(PGM5):c.49G>A(p.Glu17Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000794 in 1,385,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000079 ( 0 hom. )

Consequence

PGM5
NM_021965.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.43

Publications

1 publications found

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-AS1 (HGNC:44181): (PGM5 antisense RNA 1)

PGM5-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2434167).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021965.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PGM5	NM_021965.4	MANE Select	c.49G>A	p.Glu17Lys	missense	Exon 1 of 11	NP_068800.2	Q15124-1
PGM5-AS1	NR_015423.2		n.144+547C>T		intron	N/A
PGM5-AS1	NR_121191.1		n.264+427C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PGM5	ENST00000396396.6	TSL:2 MANE Select	c.49G>A	p.Glu17Lys	missense	Exon 1 of 11	ENSP00000379678.1	Q15124-1
PGM5	ENST00000396392.5	TSL:1	c.49G>A	p.Glu17Lys	missense	Exon 1 of 8	ENSP00000379674.1	Q15124-2
PGM5-AS1	ENST00000417887.1	TSL:1	n.130+547C>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000143

AC:

AN:

139578

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000367

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000794

AC:

AN:

1385762

Hom.:

Cov.:

AF XY:

0.0000102

AC XY:

AN XY:

683634

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31428

American (AMR)

AF:

0.00

AC:

AN:

35560

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25076

East Asian (EAS)

AF:

0.00

AC:

AN:

35660

South Asian (SAS)

AF:

0.00

AC:

AN:

79010

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39780

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4062

European-Non Finnish (NFE)

AF:

0.0000102

AC:

AN:

1077554

Other (OTH)

AF:

0.00

AC:

AN:

57632

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.092

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.89

LIST_S2

Pathogenic

0.98

M_CAP

Pathogenic

0.48

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.9

PhyloP100

1.4

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-1.5

REVEL

Benign

0.17

Sift

Benign

0.11

Sift4G

Benign

0.31

Polyphen

0.084

Vest4

0.23

MutPred

0.39

Gain of methylation at E17 (P = 0.0075)

MVP

0.41

MPC

1.8

ClinPred

0.19

GERP RS

3.1

PromoterAI

0.031

Neutral

(source)

Varity_R

0.24

gMVP

0.79

Mutation Taster

=74/26

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over