rs144102225

Variant names:

• chr9-68384446-C-A
• rs144102225
• NM_021965.4:c.473C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-68384446-C-A
• chr9-68384446-C-T

Variant summary

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

The NM_021965.4(PGM5):​c.473C>A​(p.Thr158Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,736 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T158M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PGM5 NM_021965.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.78
• 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]

ENSG00000233178 (HGNC:):

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.473C>A	p.Thr158Lys	missense	Exon 3 of 11	NP_068800.2	Q15124-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGM5	ENST00000396396.6	TSL:2 MANE Select	c.473C>A	p.Thr158Lys	missense	Exon 3 of 11	ENSP00000379678.1	Q15124-1
	PGM5	ENST00000396392.5	TSL:1	c.473C>A	p.Thr158Lys	missense	Exon 3 of 8	ENSP00000379674.1	Q15124-2
	PGM5	ENST00000902469.1		c.473C>A	p.Thr158Lys	missense	Exon 3 of 12	ENSP00000572528.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452736 Hom.: 0 Cov.: 27 AF XY: 0.00000138 AC XY: 1 AN XY: 723168

African (AFR) AF: 0.00 AC: 0 AN: 33182

American (AMR) AF: 0.00 AC: 0 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25988

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.00 AC: 0 AN: 85940

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1104242

Other (OTH) AF: 0.00 AC: 0 AN: 60050

GnomAD4 genome Cov.: 28

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	0.40
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Uncertain	0.56	D
Eigen	Benign	-0.13
Eigen_PC	Benign	0.094
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		7.8
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.27
Sift	Benign	0.35	T
Sift4G	Benign	0.49	T
Polyphen		0.0080	B
Vest4		0.80
MutPred		0.41		Gain of ubiquitination at T158 (P = 0.023)
MVP		0.42
MPC		0.29
ClinPred		0.78	D
GERP RS		4.7
Varity_R		0.39
gMVP		0.87
Mutation Taster		=37/63	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: rs144102225; hg19: chr9-70999362; COSMIC: COSV67163652;