1-63629577-T-C

Variant names:

• chr1-63629577-T-C
• rs1126727
• NM_002633.3:c.399T>C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_002633.3(PGM1):​c.399T>C​(p.Ile133Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00443 in 1,613,720 control chromosomes in the GnomAD database, including 260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. I133I) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.024 (130 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (130 hom.)
• Consequence: PGM1 NM_002633.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.00600
• Publications: 0 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 1-63629577-T-C is Benign according to our data. Variant chr1-63629577-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 297872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.006 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0814 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.399T>C	p.Ile133Ile	synonymous	Exon 2 of 11	NP_002624.2
	PGM1	NM_001172818.1		c.453T>C	p.Ile151Ile	synonymous	Exon 2 of 11	NP_001166289.1	P36871-2
	PGM1	NM_001172819.2		c.-193T>C		5_prime_UTR	Exon 2 of 11	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.399T>C	p.Ile133Ile	synonymous	Exon 2 of 11	ENSP00000360125.3	P36871-1
	PGM1	ENST00000895883.1		c.399T>C	p.Ile133Ile	synonymous	Exon 2 of 12	ENSP00000565942.1
	PGM1	ENST00000650546.1		c.399T>C	p.Ile133Ile	synonymous	Exon 2 of 12	ENSP00000497812.1	A0A3B3ITK7

Frequencies

GnomAD3 genomes AF: 0.0243 AC: 3690 AN: 152110 Hom.: 130 Cov.: 32

Gnomad AFR AF: 0.0836

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0106

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0191

GnomAD2 exomes AF: 0.00617 AC: 1528 AN: 247762 AF XY: 0.00470

Gnomad AFR exome AF: 0.0835

Gnomad AMR exome AF: 0.00498

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000207

Gnomad OTH exome AF: 0.00396

GnomAD4 exome AF: 0.00236 AC: 3444 AN: 1461492 Hom.: 130 Cov.: 32 AF XY: 0.00204 AC XY: 1483 AN XY: 727038

African (AFR) AF: 0.0819 AC: 2738 AN: 33438

American (AMR) AF: 0.00557 AC: 249 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00278 AC: 16 AN: 5764

European-Non Finnish (NFE) AF: 0.0000801 AC: 89 AN: 1111734

Other (OTH) AF: 0.00553 AC: 334 AN: 60368

GnomAD4 genome AF: 0.0243 AC: 3703 AN: 152228 Hom.: 130 Cov.: 32 AF XY: 0.0239 AC XY: 1777 AN XY: 74430

African (AFR) AF: 0.0837 AC: 3477 AN: 41522

American (AMR) AF: 0.0105 AC: 160 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68028

Other (OTH) AF: 0.0189 AC: 40 AN: 2112

Alfa AF: 0.0171 Hom.: 92

Bravo AF: 0.0276

Asia WGS AF: 0.00636 AC: 22 AN: 3476

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	PGM1-congenital disorder of glycosylation (3)
-	-	1	Congenital disorder of glycosylation (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	9.4
DANN	Benign	0.79
PhyloP100		0.0060
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: rs1126727; hg19: chr1-64095248;