1-63646195-C-T

Variant names:

• chr1-63646195-C-T
• rs3790857
• NM_002633.3:c.1145-2322C>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.1145-2322C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,012 control chromosomes in the GnomAD database, including 3,222 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 0.19 (3222 hom., cov: 32)
• Consequence: PGM1 NM_002633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.563
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGM1	NM_002633.3	c.1145-2322C>T		intron_variant	Intron 7 of 10	ENST00000371084.8	NP_002624.2
PGM1	NM_001172818.1	c.1199-2322C>T		intron_variant	Intron 7 of 10		NP_001166289.1
PGM1	NM_001172819.2	c.554-2322C>T		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.1145-2322C>T		intron_variant	Intron 7 of 10	1	NM_002633.3	ENSP00000360125.3
PGM1	ENST00000650546.1	c.1145-2322C>T		intron_variant	Intron 7 of 11			ENSP00000497812.1
PGM1	ENST00000371083.4	c.1199-2322C>T		intron_variant	Intron 7 of 10	2		ENSP00000360124.4
PGM1	ENST00000540265.5	c.554-2322C>T		intron_variant	Intron 7 of 10	2		ENSP00000443449.1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28898 AN: 151894 Hom.: 3219 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.190 AC: 28925 AN: 152012 Hom.: 3222 Cov.: 32 AF XY: 0.198 AC XY: 14740 AN XY: 74316

African (AFR) AF: 0.112 AC: 4626 AN: 41440

American (AMR) AF: 0.326 AC: 4982 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3472

East Asian (EAS) AF: 0.207 AC: 1069 AN: 5168

South Asian (SAS) AF: 0.184 AC: 885 AN: 4822

European-Finnish (FIN) AF: 0.336 AC: 3538 AN: 10540

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12698 AN: 67978

Other (OTH) AF: 0.202 AC: 426 AN: 2108

Alfa AF: 0.142 Hom.: 625

Bravo AF: 0.190

Asia WGS AF: 0.193 AC: 670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.58
DANN	Benign	0.49
PhyloP100		-0.56
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: rs3790857; hg19: chr1-64111866; COSMIC: COSV64300841;