NM_002633.3:c.1464+14G>T

Variant names:

• chr1-63651866-G-T
• rs2269238
• NM_002633.3:c.1464+14G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002633.3(PGM1):​c.1464+14G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,608,322 control chromosomes in the GnomAD database, including 38,224 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5290 hom., cov: 32)
  • Exomes 𝑓: 0.20 (32934 hom.)
• Consequence: PGM1 NM_002633.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.206
• Publications: 14 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-63651866-G-T is Benign according to our data. Variant chr1-63651866-G-T is described in ClinVar as Benign. ClinVar VariationId is 297890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.338 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.1464+14G>T		intron	N/A	NP_002624.2
	PGM1	NM_001172818.1		c.1518+14G>T		intron	N/A	NP_001166289.1	P36871-2
	PGM1	NM_001172819.2		c.873+14G>T		intron	N/A	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.1464+14G>T		intron	N/A	ENSP00000360125.3	P36871-1
	PGM1	ENST00000895882.1		c.1478G>T	p.Arg493Leu	missense	Exon 9 of 11	ENSP00000565941.1
	PGM1	ENST00000895883.1		c.1560+14G>T		intron	N/A	ENSP00000565942.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38222 AN: 151924 Hom.: 5272 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.238

GnomAD2 exomes AF: 0.244 AC: 61386 AN: 251084 AF XY: 0.232

Gnomad AFR exome AF: 0.325

Gnomad AMR exome AF: 0.433

Gnomad ASJ exome AF: 0.160

Gnomad EAS exome AF: 0.208

Gnomad FIN exome AF: 0.316

Gnomad NFE exome AF: 0.188

Gnomad OTH exome AF: 0.213

GnomAD4 exome AF: 0.204 AC: 297666 AN: 1456280 Hom.: 32934 Cov.: 29 AF XY: 0.202 AC XY: 146729 AN XY: 724750

African (AFR) AF: 0.322 AC: 10757 AN: 33362

American (AMR) AF: 0.422 AC: 18852 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 4243 AN: 26084

East Asian (EAS) AF: 0.191 AC: 7573 AN: 39628

South Asian (SAS) AF: 0.199 AC: 17144 AN: 86090

European-Finnish (FIN) AF: 0.313 AC: 16730 AN: 53380

Middle Eastern (MID) AF: 0.167 AC: 963 AN: 5756

European-Non Finnish (NFE) AF: 0.188 AC: 208679 AN: 1107070

Other (OTH) AF: 0.211 AC: 12725 AN: 60200

GnomAD4 genome AF: 0.252 AC: 38297 AN: 152042 Hom.: 5290 Cov.: 32 AF XY: 0.258 AC XY: 19184 AN XY: 74308

African (AFR) AF: 0.327 AC: 13574 AN: 41472

American (AMR) AF: 0.345 AC: 5276 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 566 AN: 3468

East Asian (EAS) AF: 0.206 AC: 1066 AN: 5172

South Asian (SAS) AF: 0.190 AC: 917 AN: 4820

European-Finnish (FIN) AF: 0.336 AC: 3545 AN: 10566

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12656 AN: 67954

Other (OTH) AF: 0.243 AC: 512 AN: 2106

Alfa AF: 0.231 Hom.: 2479

Bravo AF: 0.258

Asia WGS AF: 0.219 AC: 761 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	2	PGM1-congenital disorder of glycosylation (2)
-	-	1	Congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1
DANN	Benign	0.45
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2269238; hg19: chr1-64117537; COSMIC: COSV64300490; COSMIC: COSV64300490;