9-68357244-C-G

Variant names:

• chr9-68357244-C-G
• rs1261775217
• NM_021965.4:c.117C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021965.4(PGM5):​c.117C>G​(p.Asn39Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,543,072 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: PGM5 NM_021965.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.54
• Publications: 0 publications found

Genes affected

PGM5 (HGNC:8908): (phosphoglucomutase 5) Phosphoglucomutases (EC 5.2.2.2.), such as PGM5, are phosphotransferases involved in interconversion of glucose-1-phosphate and glucose-6-phosphate. PGM activity is essential in formation of carbohydrates from glucose-6-phosphate and in formation of glucose-6-phosphate from galactose and glycogen (Edwards et al., 1995 [PubMed 8586438]).[supplied by OMIM, Mar 2008]

PGM5-AS1 (HGNC:44181): (PGM5 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021965.4. 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
	PGM5	NM_021965.4	MANE Select	c.117C>G	p.Asn39Lys	missense	Exon 1 of 11	NP_068800.2	Q15124-1
	PGM5-AS1	NR_015423.2		n.144+479G>C		intron	N/A
	PGM5-AS1	NR_121191.1		n.264+359G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGM5	ENST00000396396.6	TSL:2 MANE Select	c.117C>G	p.Asn39Lys	missense	Exon 1 of 11	ENSP00000379678.1	Q15124-1
	PGM5	ENST00000396392.5	TSL:1	c.117C>G	p.Asn39Lys	missense	Exon 1 of 8	ENSP00000379674.1	Q15124-2
	PGM5-AS1	ENST00000417887.1	TSL:1	n.130+479G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000214 AC: 3 AN: 140310 AF XY: 0.0000394

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000410

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000183

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000122 AC: 17 AN: 1390864 Hom.: 0 Cov.: 35 AF XY: 0.0000146 AC XY: 10 AN XY: 686218

African (AFR) AF: 0.00 AC: 0 AN: 31482

American (AMR) AF: 0.0000281 AC: 1 AN: 35630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25126

East Asian (EAS) AF: 0.00 AC: 0 AN: 35700

South Asian (SAS) AF: 0.0000379 AC: 3 AN: 79064

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44064

Middle Eastern (MID) AF: 0.000492 AC: 2 AN: 4062

European-Non Finnish (NFE) AF: 0.00000928 AC: 10 AN: 1078010

Other (OTH) AF: 0.0000173 AC: 1 AN: 57726

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152208 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74348

African (AFR) AF: 0.00 AC: 0 AN: 41466

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.62	D
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.43	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.28	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		3.5
PrimateAI	Pathogenic	0.94	D
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.022	D
Polyphen		0.98	D
Vest4		0.69
MutPred		0.63		Gain of methylation at N39 (P = 0.0122)
MVP		0.32
MPC		2.7
ClinPred		0.90	D
GERP RS		2.2
PromoterAI		-0.029	Neutral
Varity_R		0.54
gMVP		0.98
Mutation Taster		=48/52	disease causing

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: rs1261775217; hg19: chr9-70972160;