NM_002633.3:c.247-316G>A

Variant names:

• chr1-63629109-G-A
• rs10489612
• NM_002633.3:c.247-316G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002633.3(PGM1):​c.247-316G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,038 control chromosomes in the GnomAD database, including 1,501 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1501 hom., cov: 32)
• Consequence: PGM1 NM_002633.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.753
• Publications: 4 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 1-63629109-G-A is Benign according to our data. Variant chr1-63629109-G-A is described in ClinVar as Benign. ClinVar VariationId is 671165.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGM1	NM_002633.3	c.247-316G>A		intron_variant	Intron 1 of 10	ENST00000371084.8	NP_002624.2
PGM1	NM_001172818.1	c.301-316G>A		intron_variant	Intron 1 of 10		NP_001166289.1
PGM1	NM_001172819.2	c.-345-316G>A		intron_variant	Intron 1 of 10		NP_001166290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGM1	ENST00000371084.8	c.247-316G>A		intron_variant	Intron 1 of 10	1	NM_002633.3	ENSP00000360125.3
PGM1	ENST00000650546.1	c.247-316G>A		intron_variant	Intron 1 of 11			ENSP00000497812.1
PGM1	ENST00000371083.4	c.301-316G>A		intron_variant	Intron 1 of 10	2		ENSP00000360124.4
PGM1	ENST00000540265.5	c.-345-316G>A		intron_variant	Intron 1 of 10	2		ENSP00000443449.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20956 AN: 151920 Hom.: 1492 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.0837

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.143

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.138 AC: 20978 AN: 152038 Hom.: 1501 Cov.: 32 AF XY: 0.138 AC XY: 10279 AN XY: 74326

African (AFR) AF: 0.189 AC: 7839 AN: 41450

American (AMR) AF: 0.132 AC: 2007 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 368 AN: 3468

East Asian (EAS) AF: 0.139 AC: 723 AN: 5186

South Asian (SAS) AF: 0.128 AC: 618 AN: 4828

European-Finnish (FIN) AF: 0.109 AC: 1156 AN: 10568

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7859 AN: 67968

Other (OTH) AF: 0.140 AC: 295 AN: 2106

Alfa AF: 0.126 Hom.: 2289

Bravo AF: 0.143

Asia WGS AF: 0.114 AC: 396 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.4
DANN	Benign	0.33
PhyloP100		0.75
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: rs10489612; hg19: chr1-64094780; COSMIC: COSV64300324;