chr9-68378322-G-A

Position:

• chr9-68378322-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021965.4(PGM5):​c.385G>A​(p.Gly129Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 29)
• Consequence: PGM5 NM_021965.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.52

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29907882).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGM5	NM_021965.4	c.385G>A	p.Gly129Arg	missense_variant	2/11	ENST00000396396.6	NP_068800.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGM5	ENST00000396396.6	c.385G>A	p.Gly129Arg	missense_variant	2/11	2	NM_021965.4	ENSP00000379678.1
PGM5	ENST00000396392.5	c.385G>A	p.Gly129Arg	missense_variant	2/8	1		ENSP00000379674.1
PGM5	ENST00000431583.1	c.283G>A	p.Gly95Arg	missense_variant	2/4	5		ENSP00000394864.1
PGM5	ENST00000604870.6	n.740G>A		non_coding_transcript_exon_variant	5/12	5

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 29

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 26, 2024

The c.385G>A (p.G129R) alteration is located in exon 2 (coding exon 2) of the PGM5 gene. This alteration results from a G to A substitution at nucleotide position 385, causing the glycine (G) at amino acid position 129 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	.;T;T
Eigen	Benign	0.025
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.1	L;L;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.46	N;N;N
REVEL	Benign	0.10
Sift	Benign	0.082	T;D;D
Sift4G	Uncertain	0.034	D;D;T
Polyphen		0.15	.;B;.
Vest4		0.46
MutPred		0.41		Gain of methylation at G129 (P = 0.0349);Gain of methylation at G129 (P = 0.0349);.;
MVP		0.17
MPC		2.2
ClinPred		0.90	D
GERP RS		4.4
Varity_R		0.15
gMVP		0.89

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: rs782658485; hg19: chr9-70993238;