rs2269239

Variant names:

• chr1-63643688-C-G
• rs2269239
• NM_002633.3:c.1145-4829C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-63643688-C-G
• chr1-63643688-C-T

Variant summary

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

The NM_002633.3(PGM1):​c.1145-4829C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,186 control chromosomes in the GnomAD database, including 3,814 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 0.21 (3814 hom., cov: 33)
• Consequence: PGM1 NM_002633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGM1	NM_002633.3	c.1145-4829C>G		intron_variant	Intron 7 of 10	ENST00000371084.8	NP_002624.2
PGM1	NM_001172818.1	c.1199-4829C>G		intron_variant	Intron 7 of 10		NP_001166289.1
PGM1	NM_001172819.2	c.554-4829C>G		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.1145-4829C>G		intron_variant	Intron 7 of 10	1	NM_002633.3	ENSP00000360125.3
PGM1	ENST00000650546.1	c.1145-4829C>G		intron_variant	Intron 7 of 11			ENSP00000497812.1
PGM1	ENST00000371083.4	c.1199-4829C>G		intron_variant	Intron 7 of 10	2		ENSP00000360124.4
PGM1	ENST00000540265.5	c.554-4829C>G		intron_variant	Intron 7 of 10	2		ENSP00000443449.1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32605 AN: 152068 Hom.: 3805 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.215 AC: 32658 AN: 152186 Hom.: 3814 Cov.: 33 AF XY: 0.221 AC XY: 16473 AN XY: 74386

African (AFR) AF: 0.182 AC: 7553 AN: 41546

American (AMR) AF: 0.336 AC: 5140 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 570 AN: 3466

East Asian (EAS) AF: 0.207 AC: 1071 AN: 5174

South Asian (SAS) AF: 0.187 AC: 904 AN: 4826

European-Finnish (FIN) AF: 0.337 AC: 3565 AN: 10576

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13235 AN: 68002

Other (OTH) AF: 0.219 AC: 464 AN: 2114

Alfa AF: 0.208 Hom.: 425

Bravo AF: 0.216

Asia WGS AF: 0.201 AC: 698 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.5
DANN	Benign	0.73
PhyloP100		-0.029
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: rs2269239; hg19: chr1-64109359;