1-63651866-G-T

Position:

• chr1-63651866-G-T

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.1464+14G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,608,322 control chromosomes in the GnomAD database, including 38,224 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5290 hom., cov: 32)
  • Exomes 𝑓: 0.20 (32934 hom.)
• Consequence: PGM1 NM_002633.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.206

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=-0.92).
• BP6: Variant 1-63651866-G-T is Benign according to our data. Variant chr1-63651866-G-T is described in ClinVar as [Benign]. Clinvar id is 297890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGM1	NM_002633.3	c.1464+14G>T		intron_variant		ENST00000371084.8
PGM1	NM_001172818.1	c.1518+14G>T		intron_variant
PGM1	NM_001172819.2	c.873+14G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGM1	ENST00000371084.8	c.1464+14G>T		intron_variant		1	NM_002633.3	P1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38222 AN: 151924 Hom.: 5272 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.238

GnomAD3 exomes AF: 0.244 AC: 61386 AN: 251084 Hom.: 8742 AF XY: 0.232 AC XY: 31497 AN XY: 135712

Gnomad AFR exome AF: 0.325

Gnomad AMR exome AF: 0.433

Gnomad ASJ exome AF: 0.160

Gnomad EAS exome AF: 0.208

Gnomad SAS exome AF: 0.202

Gnomad FIN exome AF: 0.316

Gnomad NFE exome AF: 0.188

Gnomad OTH exome AF: 0.213

GnomAD4 exome AF: 0.204 AC: 297666 AN: 1456280 Hom.: 32934 Cov.: 29 AF XY: 0.202 AC XY: 146729 AN XY: 724750

Gnomad4 AFR exome AF: 0.322

Gnomad4 AMR exome AF: 0.422

Gnomad4 ASJ exome AF: 0.163

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.199

Gnomad4 FIN exome AF: 0.313

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.211

GnomAD4 genome AF: 0.252 AC: 38297 AN: 152042 Hom.: 5290 Cov.: 32 AF XY: 0.258 AC XY: 19184 AN XY: 74308

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.243

Alfa AF: 0.178 Hom.: 797

Bravo AF: 0.258

Asia WGS AF: 0.219 AC: 761 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 02, 2015	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. -
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 62% of patients studied by a panel of primary immunodeficiencies. Number of patients: 59. Only high quality variants are reported. -

not provided Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 23, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

PGM1-congenital disorder of glycosylation Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Congenital disorder of glycosylation Benign:1

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	-0.92
CADD	Benign	3.1
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2269238; hg19: chr1-64117537; COSMIC: COSV64300490; COSMIC: COSV64300490;