rs855315

Variant names:

• chr1-63603941-A-G
• rs855315
• NM_002633.3:c.246+10207A>G

Variant summary

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

The NM_002633.3(PGM1):​c.246+10207A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,030 control chromosomes in the GnomAD database, including 8,993 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 0.34 (8993 hom., cov: 32)
• Consequence: PGM1 NM_002633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• Publications: 10 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGM1	NM_002633.3	c.246+10207A>G		intron_variant	Intron 1 of 10	ENST00000371084.8	NP_002624.2
PGM1	NM_001172819.2	c.-346+9797A>G		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.246+10207A>G		intron_variant	Intron 1 of 10	1	NM_002633.3	ENSP00000360125.3
PGM1	ENST00000650546.1	c.246+10207A>G		intron_variant	Intron 1 of 11			ENSP00000497812.1
PGM1	ENST00000540265.5	c.-346+9797A>G		intron_variant	Intron 1 of 10	2		ENSP00000443449.1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51804 AN: 151916 Hom.: 8987 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.341 AC: 51823 AN: 152030 Hom.: 8993 Cov.: 32 AF XY: 0.343 AC XY: 25511 AN XY: 74296

African (AFR) AF: 0.299 AC: 12397 AN: 41458

American (AMR) AF: 0.447 AC: 6825 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1165 AN: 3468

East Asian (EAS) AF: 0.483 AC: 2493 AN: 5158

South Asian (SAS) AF: 0.480 AC: 2313 AN: 4822

European-Finnish (FIN) AF: 0.305 AC: 3224 AN: 10568

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22295 AN: 67968

Other (OTH) AF: 0.335 AC: 707 AN: 2110

Alfa AF: 0.341 Hom.: 7120

Bravo AF: 0.349

Asia WGS AF: 0.467 AC: 1627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.8
DANN	Benign	0.49
PhyloP100		-0.0070
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: rs855315; hg19: chr1-64069612; COSMIC: COSV107463367; COSMIC: COSV107463367;