1-63648510-C-G

Variant names:

• chr1-63648510-C-G
• rs72922609
• NM_002633.3:c.1145-7C>G

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.1145-7C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00759 in 1,614,016 control chromosomes in the GnomAD database, including 782 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 0.040 (407 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (375 hom.)
• Consequence: PGM1 NM_002633.3 splice_region, intron
• Scores: Splicing: ADA: 0.0003883
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.172

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=-0.84).
• BP6: Variant 1-63648510-C-G is Benign according to our data. Variant chr1-63648510-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 297883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGM1	NM_002633.3	c.1145-7C>G		splice_region_variant, intron_variant	Intron 7 of 10	ENST00000371084.8	NP_002624.2
PGM1	NM_001172818.1	c.1199-7C>G		splice_region_variant, intron_variant	Intron 7 of 10		NP_001166289.1
PGM1	NM_001172819.2	c.554-7C>G		splice_region_variant, intron_variant	Intron 7 of 10		NP_001166290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGM1	ENST00000371084.8	c.1145-7C>G		splice_region_variant, intron_variant	Intron 7 of 10	1	NM_002633.3	ENSP00000360125.3
PGM1	ENST00000650546.1	c.1145-7C>G		splice_region_variant, intron_variant	Intron 7 of 11			ENSP00000497812.1
PGM1	ENST00000371083.4	c.1199-7C>G		splice_region_variant, intron_variant	Intron 7 of 10	2		ENSP00000360124.4
PGM1	ENST00000540265.5	c.554-7C>G		splice_region_variant, intron_variant	Intron 7 of 10	2		ENSP00000443449.1

Frequencies

GnomAD3 genomes AF: 0.0401 AC: 6097 AN: 152140 Hom.: 407 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0122

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: 0.000367

Gnomad OTH AF: 0.0249

GnomAD3 exomes AF: 0.0106 AC: 2650 AN: 250818 Hom.: 174 AF XY: 0.00757 AC XY: 1027 AN XY: 135584

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.00648

Gnomad ASJ exome AF: 0.00109

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000327

Gnomad OTH exome AF: 0.00425

GnomAD4 exome AF: 0.00420 AC: 6146 AN: 1461758 Hom.: 375 Cov.: 32 AF XY: 0.00366 AC XY: 2665 AN XY: 727182

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.00702

Gnomad4 ASJ exome AF: 0.00130

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000267

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000296

Gnomad4 OTH exome AF: 0.00835

GnomAD4 genome AF: 0.0401 AC: 6111 AN: 152258 Hom.: 407 Cov.: 32 AF XY: 0.0390 AC XY: 2900 AN XY: 74446

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.0122

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.00234 Hom.: 1

Bravo AF: 0.0445

Asia WGS AF: 0.00866 AC: 31 AN: 3478

EpiCase AF: 0.000818

EpiControl AF: 0.000356

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

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

- -

Mar 14, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PGM1-congenital disorder of glycosylation Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely 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	-0.84
CADD	Benign	0.27
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00039
dbscSNV1_RF	Benign	0.030
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: rs72922609; hg19: chr1-64114181;