NM_002633.3:c.1145-7C>G

Variant names:

• chr1-63648510-C-G
• rs72922609
• NM_002633.3:c.1145-7C>G

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.1145-7C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00759 in 1,614,016 control chromosomes in the GnomAD database, including 782 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.040 (407 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (375 hom.)
• Consequence: PGM1 NM_002633.3 splice_region, intron
• Scores: Splicing: ADA: 0.0003883
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.172
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-63648510-C-G is Benign according to our data. Variant chr1-63648510-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 297883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 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.1145-7C>G		splice_region intron	N/A	NP_002624.2
	PGM1	NM_001172818.1		c.1199-7C>G		splice_region intron	N/A	NP_001166289.1
	PGM1	NM_001172819.2		c.554-7C>G		splice_region 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.1145-7C>G		splice_region intron	N/A	ENSP00000360125.3
	PGM1	ENST00000895883.1		c.1241-7C>G		splice_region intron	N/A	ENSP00000565942.1
	PGM1	ENST00000650546.1		c.1145-7C>G		splice_region intron	N/A	ENSP00000497812.1

Frequencies

GnomAD3 genomes AF: 0.0401 AC: 6097 AN: 152140 Hom.: 407 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0249

GnomAD2 exomes AF: 0.0106 AC: 2650 AN: 250818 AF XY: 0.00757

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.00648

Gnomad ASJ exome AF: 0.00109

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000327

Gnomad OTH exome AF: 0.00425

GnomAD4 exome AF: 0.00420 AC: 6146 AN: 1461758 Hom.: 375 Cov.: 32 AF XY: 0.00366 AC XY: 2665 AN XY: 727182

African (AFR) AF: 0.146 AC: 4891 AN: 33472

American (AMR) AF: 0.00702 AC: 314 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00130 AC: 34 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.000267 AC: 23 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00884 AC: 51 AN: 5766

European-Non Finnish (NFE) AF: 0.000296 AC: 329 AN: 1111954

Other (OTH) AF: 0.00835 AC: 504 AN: 60386

GnomAD4 genome AF: 0.0401 AC: 6111 AN: 152258 Hom.: 407 Cov.: 32 AF XY: 0.0390 AC XY: 2900 AN XY: 74446

African (AFR) AF: 0.141 AC: 5844 AN: 41536

American (AMR) AF: 0.0122 AC: 186 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 68024

Other (OTH) AF: 0.0246 AC: 52 AN: 2110

Alfa AF: 0.00234 Hom.: 1

Bravo AF: 0.0445

Asia WGS AF: 0.00866 AC: 31 AN: 3478

EpiCase AF: 0.000818

EpiControl AF: 0.000356

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.27
DANN	Benign	0.43
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00039
dbscSNV1_RF	Benign	0.030
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: rs72922609; hg19: chr1-64114181;