NM_002633.3:c.*93A>C

Variant names:

• chr1-63659768-A-C
• rs4643
• NM_002633.3:c.*93A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002633.3(PGM1):​c.*93A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 949,000 control chromosomes in the GnomAD database, including 18,877 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2651 hom., cov: 32)
  • Exomes 𝑓: 0.19 (16226 hom.)
• Consequence: PGM1 NM_002633.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.192
• Publications: 25 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-63659768-A-C is Benign according to our data. Variant chr1-63659768-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 297897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGM1	NM_002633.3	c.*93A>C		3_prime_UTR_variant	Exon 11 of 11	ENST00000371084.8	NP_002624.2
PGM1	NM_001172818.1	c.*93A>C		3_prime_UTR_variant	Exon 11 of 11		NP_001166289.1
PGM1	NM_001172819.2	c.*93A>C		3_prime_UTR_variant	Exon 11 of 11		NP_001166290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGM1	ENST00000371084.8	c.*93A>C		3_prime_UTR_variant	Exon 11 of 11	1	NM_002633.3	ENSP00000360125.3
PGM1	ENST00000650546.1	c.*149A>C		3_prime_UTR_variant	Exon 12 of 12			ENSP00000497812.1
PGM1	ENST00000371083.4	c.*93A>C		3_prime_UTR_variant	Exon 11 of 11	2		ENSP00000360124.4
PGM1	ENST00000540265.5	c.*93A>C		3_prime_UTR_variant	Exon 11 of 11	2		ENSP00000443449.1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26500 AN: 152054 Hom.: 2651 Cov.: 32

Gnomad AFR AF: 0.0890

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.201

GnomAD4 exome AF: 0.195 AC: 155065 AN: 796828 Hom.: 16226 Cov.: 11 AF XY: 0.194 AC XY: 80979 AN XY: 418038

African (AFR) AF: 0.0810 AC: 1671 AN: 20620

American (AMR) AF: 0.332 AC: 13110 AN: 39516

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 3182 AN: 21592

East Asian (EAS) AF: 0.193 AC: 6828 AN: 35288

South Asian (SAS) AF: 0.191 AC: 13407 AN: 70228

European-Finnish (FIN) AF: 0.266 AC: 13480 AN: 50730

Middle Eastern (MID) AF: 0.155 AC: 704 AN: 4556

European-Non Finnish (NFE) AF: 0.184 AC: 95104 AN: 515902

Other (OTH) AF: 0.197 AC: 7579 AN: 38396

GnomAD4 genome AF: 0.174 AC: 26519 AN: 152172 Hom.: 2651 Cov.: 32 AF XY: 0.179 AC XY: 13350 AN XY: 74386

African (AFR) AF: 0.0889 AC: 3695 AN: 41544

American (AMR) AF: 0.283 AC: 4323 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 517 AN: 3470

East Asian (EAS) AF: 0.213 AC: 1099 AN: 5166

South Asian (SAS) AF: 0.178 AC: 860 AN: 4820

European-Finnish (FIN) AF: 0.277 AC: 2931 AN: 10566

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12470 AN: 68004

Other (OTH) AF: 0.202 AC: 427 AN: 2112

Alfa AF: 0.179 Hom.: 8315

Bravo AF: 0.172

Asia WGS AF: 0.197 AC: 684 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 38% of patients studied by a panel of primary immunodeficiencies. Number of patients: 36. Only high quality variants are reported. -

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

- -

PGM1-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	-0.82
CADD	Benign	9.7
DANN	Benign	0.67
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4643; hg19: chr1-64125439;