1-63659768-A-T

Variant names:

• chr1-63659768-A-T
• rs4643
• NM_002633.3:c.*93A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002633.3(PGM1):​c.*93A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000251 in 797,650 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: PGM1 NM_002633.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGM1	NM_002633.3	c.*93A>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000371084.8	NP_002624.2
PGM1	NM_001172818.1	c.*93A>T		3_prime_UTR_variant	Exon 11 of 11		NP_001166289.1
PGM1	NM_001172819.2	c.*93A>T		3_prime_UTR_variant	Exon 11 of 11		NP_001166290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGM1	ENST00000371084.8	c.*93A>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_002633.3	ENSP00000360125.3
PGM1	ENST00000650546.1	c.*149A>T		3_prime_UTR_variant	Exon 12 of 12			ENSP00000497812.1
PGM1	ENST00000371083.4	c.*93A>T		3_prime_UTR_variant	Exon 11 of 11	2		ENSP00000360124.4
PGM1	ENST00000540265.5	c.*93A>T		3_prime_UTR_variant	Exon 11 of 11	2		ENSP00000443449.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000251 AC: 2 AN: 797650 Hom.: 0 Cov.: 11 AF XY: 0.00000478 AC XY: 2 AN XY: 418436

African (AFR) AF: 0.00 AC: 0 AN: 20638

American (AMR) AF: 0.00 AC: 0 AN: 39526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21594

East Asian (EAS) AF: 0.0000567 AC: 2 AN: 35296

South Asian (SAS) AF: 0.00 AC: 0 AN: 70248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50780

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4556

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 516580

Other (OTH) AF: 0.00 AC: 0 AN: 38432

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.6
DANN	Benign	0.79
PhyloP100		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4643; hg19: chr1-64125439;