rs72922610

Variant names:

Variant summary

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

The NM_002633.3(PGM1):c.1280+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00496 in 1,613,570 control chromosomes in the GnomAD database, including 313 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 158 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 155 hom. )

Consequence

PGM1
NM_002633.3 splice_region, intron

Scores

Splicing: ADA: 0.00003664

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.32

Publications

1 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: Genomics England PanelApp, Ambry Genetics, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), Orphanet

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 (BayesDel_noAF=-0.78).

BP6

Variant 1-63648659-C-T is Benign according to our data. Variant chr1-63648659-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 297886.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PGM1	NM_002633.3 link	c.1280+7C>T	splice_region_variant, intron_variant	Intron 8 of 10	ENST00000371084.8	NP_002624.2	P36871-1
PGM1	NM_001172818.1 link	c.1334+7C>T	splice_region_variant, intron_variant	Intron 8 of 10		NP_001166289.1	P36871-2B7Z6C2
PGM1	NM_001172819.2 link	c.689+7C>T	splice_region_variant, intron_variant	Intron 8 of 10		NP_001166290.1	P36871-3B4DDQ8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PGM1	ENST00000371084.8 link	c.1280+7C>T	splice_region_variant, intron_variant	Intron 8 of 10	1	NM_002633.3	ENSP00000360125.3	P36871-1
PGM1	ENST00000650546.1 link	c.1280+7C>T	splice_region_variant, intron_variant	Intron 8 of 11			ENSP00000497812.1	A0A3B3ITK7
PGM1	ENST00000371083.4 link	c.1334+7C>T	splice_region_variant, intron_variant	Intron 8 of 10	2		ENSP00000360124.4	P36871-2
PGM1	ENST00000540265.5 link	c.689+7C>T	splice_region_variant, intron_variant	Intron 8 of 10	2		ENSP00000443449.1	P36871-3

Frequencies

GnomAD3 genomes

AF:

0.0259

AC:

3947

AN:

152148

Hom.:

157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0909

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00798

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0187

GnomAD2 exomes

AF:

0.00697

AC:

1747

AN:

250710

AF XY:

0.00516

show subpopulations

Gnomad AFR exome

AF:

0.0938

Gnomad AMR exome

AF:

0.00497

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00277

AC:

4044

AN:

1461304

Hom.:

155

Cov.:

AF XY:

0.00248

AC XY:

1806

AN XY:

726972

show subpopulations

African (AFR)

AF:

0.0940

AC:

3147

AN:

33464

American (AMR)

AF:

0.00512

AC:

229

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00130

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.000197

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53270

Middle Eastern (MID)

AF:

0.00679

AC:

AN:

5594

European-Non Finnish (NFE)

AF:

0.000213

AC:

237

AN:

1111854

Other (OTH)

AF:

0.00567

AC:

342

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

206

412

619

825

1031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

216

324

432

540

<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:

0.0260

AC:

3959

AN:

152266

Hom.:

158

Cov.:

AF XY:

0.0254

AC XY:

1890

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0910

AC:

3778

AN:

41536

American (AMR)

AF:

0.00797

AC:

122

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68026

Other (OTH)

AF:

0.0185

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

175

349

524

698

873

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.0141

Hom.:

Bravo

AF:

0.0286

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 14, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

PGM1-congenital disorder of glycosylation

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 15, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Congenital disorder of glycosylation

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.84

(source)

DANN

Benign

0.48

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000037

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.020

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over