rs2269260

Variant names:

• chr1-63619666-G-A
• rs2269260
• NM_002633.3:c.247-9759G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002633.3(PGM1):​c.247-9759G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,102 control chromosomes in the GnomAD database, including 1,388 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1388 hom., cov: 32)
• Consequence: PGM1 NM_002633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.162
• Publications: 7 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: G2P, Orphanet, Genomics England PanelApp, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002633.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGM1	NM_002633.3	MANE Select	c.247-9759G>A		intron	N/A	NP_002624.2
	PGM1	NM_001172819.2		c.-345-9759G>A		intron	N/A	NP_001166290.1	P36871-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGM1	ENST00000371084.8	TSL:1 MANE Select	c.247-9759G>A		intron	N/A	ENSP00000360125.3	P36871-1
	PGM1	ENST00000895883.1		c.247-9759G>A		intron	N/A	ENSP00000565942.1
	PGM1	ENST00000650546.1		c.247-9759G>A		intron	N/A	ENSP00000497812.1	A0A3B3ITK7

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19344 AN: 151984 Hom.: 1387 Cov.: 32

Gnomad AFR AF: 0.0892

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0730

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.127 AC: 19358 AN: 152102 Hom.: 1388 Cov.: 32 AF XY: 0.131 AC XY: 9730 AN XY: 74336

African (AFR) AF: 0.0893 AC: 3709 AN: 41512

American (AMR) AF: 0.0729 AC: 1114 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 366 AN: 3470

East Asian (EAS) AF: 0.125 AC: 646 AN: 5164

South Asian (SAS) AF: 0.107 AC: 514 AN: 4814

European-Finnish (FIN) AF: 0.257 AC: 2709 AN: 10538

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9943 AN: 68002

Other (OTH) AF: 0.122 AC: 257 AN: 2110

Alfa AF: 0.132 Hom.: 2383

Bravo AF: 0.114

Asia WGS AF: 0.100 AC: 346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.61
PhyloP100		-0.16
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: rs2269260; hg19: chr1-64085337;