NM_002633.3:c.1144+4300T>C

Variant names:

• chr1-63643100-T-C
• rs2269241
• NM_002633.3:c.1144+4300T>C

Variant summary

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

The NM_002633.3(PGM1):​c.1144+4300T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,128 control chromosomes in the GnomAD database, including 4,278 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 0.23 (4278 hom., cov: 32)
• Consequence: PGM1 NM_002633.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397
• Publications: 36 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.333 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGM1	NM_002633.3	MANE Select	c.1144+4300T>C		intron	N/A	NP_002624.2
	PGM1	NM_001172818.1		c.1198+4300T>C		intron	N/A	NP_001166289.1
	PGM1	NM_001172819.2		c.553+4300T>C		intron	N/A	NP_001166290.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGM1	ENST00000371084.8	TSL:1 MANE Select	c.1144+4300T>C		intron	N/A	ENSP00000360125.3
	PGM1	ENST00000650546.1		c.1144+4300T>C		intron	N/A	ENSP00000497812.1
	PGM1	ENST00000371083.4	TSL:2	c.1198+4300T>C		intron	N/A	ENSP00000360124.4

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34826 AN: 152010 Hom.: 4263 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.229 AC: 34892 AN: 152128 Hom.: 4278 Cov.: 32 AF XY: 0.236 AC XY: 17529 AN XY: 74346

African (AFR) AF: 0.232 AC: 9642 AN: 41524

American (AMR) AF: 0.341 AC: 5215 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 570 AN: 3470

East Asian (EAS) AF: 0.210 AC: 1081 AN: 5146

South Asian (SAS) AF: 0.188 AC: 908 AN: 4822

European-Finnish (FIN) AF: 0.338 AC: 3574 AN: 10564

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

European-Non Finnish (NFE) AF: 0.195 AC: 13258 AN: 68000

Other (OTH) AF: 0.231 AC: 488 AN: 2110

Alfa AF: 0.210 Hom.: 7593

Bravo AF: 0.233

Asia WGS AF: 0.214 AC: 742 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.8
DANN	Benign	0.67
PhyloP100		-0.40
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: rs2269241; hg19: chr1-64108771;