rs855314

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001172819.2(PGM1):c.-330A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.143 in 1,611,504 control chromosomes in the GnomAD database, including 17,798 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2331 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15467 hom. )

Consequence

PGM1
NM_001172819.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 9.20

Publications

23 publications found

Variant links:

Genes affected

PGM1 (HGNC:8905): (phosphoglucomutase 1) The protein encoded by this gene is an isozyme of phosphoglucomutase (PGM) and belongs to the phosphohexose mutase family. There are several PGM isozymes, which are encoded by different genes and catalyze the transfer of phosphate between the 1 and 6 positions of glucose. In most cell types, this PGM isozyme is predominant, representing about 90% of total PGM activity. In red cells, PGM2 is a major isozyme. This gene is highly polymorphic. Mutations in this gene cause glycogen storage disease type 14. Alternativley spliced transcript variants encoding different isoforms have been identified in this gene.[provided by RefSeq, Mar 2010]

PGM1 Gene-Disease associations (from GenCC):

PGM1-congenital disorder of glycosylation
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Genomics England PanelApp, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

PGM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002285391).

BP6

Variant 1-63629440-A-G is Benign according to our data. Variant chr1-63629440-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 297871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172819.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PGM1	NM_002633.3	MANE Select	c.262A>G	p.Ile88Val	missense	Exon 2 of 11	NP_002624.2
PGM1	NM_001172819.2		c.-330A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 11	NP_001166290.1	P36871-3
PGM1	NM_001172818.1		c.316A>G	p.Ile106Val	missense	Exon 2 of 11	NP_001166289.1	P36871-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PGM1	ENST00000371084.8	TSL:1 MANE Select	c.262A>G	p.Ile88Val	missense	Exon 2 of 11	ENSP00000360125.3	P36871-1
PGM1	ENST00000540265.5	TSL:2	c.-330A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 11	ENSP00000443449.1	P36871-3
PGM1	ENST00000895883.1		c.262A>G	p.Ile88Val	missense	Exon 2 of 12	ENSP00000565942.1

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24762

AN:

151950

Hom.:

2322

Cov.:

show subpopulations

Gnomad AFR

AF:

0.245

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.111

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.00867

Gnomad SAS

AF:

0.0907

Gnomad FIN

AF:

0.128

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.172

GnomAD2 exomes

AF:

0.125

AC:

31190

AN:

248928

AF XY:

0.125

show subpopulations

Gnomad AFR exome

AF:

0.247

Gnomad AMR exome

AF:

0.0696

Gnomad ASJ exome

AF:

0.131

Gnomad EAS exome

AF:

0.00718

Gnomad FIN exome

AF:

0.132

Gnomad NFE exome

AF:

0.151

Gnomad OTH exome

AF:

0.129

GnomAD4 exome

AF:

0.140

AC:

204850

AN:

1459436

Hom.:

15467

Cov.:

AF XY:

0.139

AC XY:

101033

AN XY:

726132

show subpopulations

African (AFR)

AF:

0.255

AC:

8519

AN:

33394

American (AMR)

AF:

0.0745

AC:

3332

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.133

AC:

3471

AN:

26106

East Asian (EAS)

AF:

0.00428

AC:

170

AN:

39692

South Asian (SAS)

AF:

0.0986

AC:

8505

AN:

86218

European-Finnish (FIN)

AF:

0.130

AC:

6930

AN:

53414

Middle Eastern (MID)

AF:

0.191

AC:

1099

AN:

5750

European-Non Finnish (NFE)

AF:

0.148

AC:

164358

AN:

1109830

Other (OTH)

AF:

0.140

AC:

8466

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

8384

16768

25153

33537

41921

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5826

11652

17478

23304

29130

<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

AF:

0.163

AC:

24806

AN:

152068

Hom.:

2331

Cov.:

AF XY:

0.160

AC XY:

11904

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.245

AC:

10167

AN:

41460

American (AMR)

AF:

0.111

AC:

1692

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

477

AN:

3470

East Asian (EAS)

AF:

0.00908

AC:

AN:

5178

South Asian (SAS)

AF:

0.0908

AC:

437

AN:

4812

European-Finnish (FIN)

AF:

0.128

AC:

1358

AN:

10582

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.148

AC:

10092

AN:

67968

Other (OTH)

AF:

0.170

AC:

358

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1022

2043

3065

4086

5108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

268

536

804

1072

1340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.150

Hom.:

5205

Bravo

AF:

0.164

TwinsUK

AF:

0.149

AC:

553

ALSPAC

AF:

0.147

AC:

567

ESP6500AA

AF:

0.240

AC:

1057

ESP6500EA

AF:

0.141

AC:

1212

ExAC

AF:

0.130

AC:

15834

Asia WGS

AF:

0.0700

AC:

245

AN:

3478

EpiCase

AF:

0.147

EpiControl

AF:

0.151

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (2)

PGM1-congenital disorder of glycosylation (2)

Congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.38

Eigen

Benign

-0.23

Eigen_PC

Benign

0.044

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

MetaRNN

Benign

0.0023

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.74

PhyloP100

9.2

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.030

REVEL

Benign

0.19

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.11

Vest4

0.34

MPC

0.64

ClinPred

0.035

GERP RS

5.5

Varity_R

0.14

gMVP

0.55

Mutation Taster

=55/45

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over