9-68384437-T-C

Position:

• chr9-68384437-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021965.4(PGM5):​c.464T>C​(p.Ile155Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 28)
• Consequence: PGM5 NM_021965.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.89

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGM5	NM_021965.4	c.464T>C	p.Ile155Thr	missense_variant	3/11	ENST00000396396.6	NP_068800.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGM5	ENST00000396396.6	c.464T>C	p.Ile155Thr	missense_variant	3/11	2	NM_021965.4	ENSP00000379678.1
PGM5	ENST00000396392.5	c.464T>C	p.Ile155Thr	missense_variant	3/8	1		ENSP00000379674.1
PGM5	ENST00000431583.1	c.323-3026T>C		intron_variant		5		ENSP00000394864.1
PGM5	ENST00000604870.6	n.819T>C		non_coding_transcript_exon_variant	6/12	5

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 28

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 11, 2024

The c.464T>C (p.I155T) alteration is located in exon 3 (coding exon 3) of the PGM5 gene. This alteration results from a T to C substitution at nucleotide position 464, causing the isoleucine (I) at amino acid position 155 to be replaced by a threonine (T). 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	Pathogenic	0.57
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	.;D
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.6	D;D
REVEL	Benign	0.26
Sift	Benign	0.42	T;T
Sift4G	Benign	0.47	T;T
Polyphen		0.66	.;P
Vest4		0.67
MutPred		0.47		Loss of stability (P = 0.017);Loss of stability (P = 0.017);
MVP		0.13
MPC		0.76
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.33
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-70999353;