rs2269241

Positions:

• chr1-63643100-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGM1	NM_002633.3	c.1144+4300T>C		intron_variant		ENST00000371084.8	NP_002624.2
PGM1	NM_001172818.1	c.1198+4300T>C		intron_variant			NP_001166289.1
PGM1	NM_001172819.2	c.553+4300T>C		intron_variant			NP_001166290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGM1	ENST00000371084.8	c.1144+4300T>C		intron_variant		1	NM_002633.3	ENSP00000360125.3
PGM1	ENST00000650546.1	c.1144+4300T>C		intron_variant				ENSP00000497812.1
PGM1	ENST00000371083.4	c.1198+4300T>C		intron_variant		2		ENSP00000360124.4
PGM1	ENST00000540265.5	c.553+4300T>C		intron_variant		2		ENSP00000443449.1

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

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.231

Alfa AF: 0.201 Hom.: 3961

Bravo AF: 0.233

Asia WGS AF: 0.214 AC: 742 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.8
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs2269241; hg19: chr1-64108771;