rs4643

Positions:

• chr1-63659768-A-C

Variant summary

Our verdict is Benign. Variant got -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:4
• Conservation: PhyloP100: 0.192

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]

ACMG classification

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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/exons	MANE	UniProt
PGM1	NM_002633.3	c.*93A>C		3_prime_UTR_variant	11/11	ENST00000371084.8
PGM1	NM_001172818.1	c.*93A>C		3_prime_UTR_variant	11/11
PGM1	NM_001172819.2	c.*93A>C		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGM1	ENST00000371084.8	c.*93A>C		3_prime_UTR_variant	11/11	1	NM_002633.3	P1
PGM1	ENST00000371083.4	c.*93A>C		3_prime_UTR_variant	11/11	2
PGM1	ENST00000540265.5	c.*93A>C		3_prime_UTR_variant	11/11	2
PGM1	ENST00000650546.1	c.*149A>C		3_prime_UTR_variant	12/12

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

Gnomad4 AFR exome AF: 0.0810

Gnomad4 AMR exome AF: 0.332

Gnomad4 ASJ exome AF: 0.147

Gnomad4 EAS exome AF: 0.193

Gnomad4 SAS exome AF: 0.191

Gnomad4 FIN exome AF: 0.266

Gnomad4 NFE exome AF: 0.184

Gnomad4 OTH exome AF: 0.197

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

Gnomad4 AFR AF: 0.0889

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.202

Alfa AF: 0.182 Hom.: 5329

Bravo AF: 0.172

Asia WGS AF: 0.197 AC: 684 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

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

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

- -

PGM1-congenital disorder of glycosylation Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.7
DANN	Benign	0.67

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

Other links and lift over

dbSNP: rs4643; hg19: chr1-64125439;