9-68357348-C-A

Variant names:

• chr9-68357348-C-A
• rs1554675820
• NM_021965.4:c.221C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021965.4(PGM5):​c.221C>A​(p.Thr74Lys) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PGM5 NM_021965.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.77
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22616601).

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.221C>A	p.Thr74Lys	missense	Exon 1 of 11	NP_068800.2	Q15124-1
	PGM5-AS1	NR_015423.2		n.144+375G>T		intron	N/A
	PGM5-AS1	NR_121191.1		n.264+255G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGM5	ENST00000396396.6	TSL:2 MANE Select	c.221C>A	p.Thr74Lys	missense	Exon 1 of 11	ENSP00000379678.1	Q15124-1
	PGM5	ENST00000396392.5	TSL:1	c.221C>A	p.Thr74Lys	missense	Exon 1 of 8	ENSP00000379674.1	Q15124-2
	PGM5-AS1	ENST00000417887.1	TSL:1	n.130+375G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.10e-7 AC: 1 AN: 1408788 Hom.: 0 Cov.: 34 AF XY: 0.00000144 AC XY: 1 AN XY: 696668

African (AFR) AF: 0.00 AC: 0 AN: 31934

American (AMR) AF: 0.00 AC: 0 AN: 37838

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25302

East Asian (EAS) AF: 0.0000275 AC: 1 AN: 36390

South Asian (SAS) AF: 0.00 AC: 0 AN: 80124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46826

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4088

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1087932

Other (OTH) AF: 0.00 AC: 0 AN: 58354

GnomAD4 genome Cov.: 32

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	Benign	0.12
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.26	N
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.8
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	0.36	N
REVEL	Benign	0.14
Sift	Benign	0.041	D
Sift4G	Benign	0.15	T
Polyphen		0.30	B
Vest4		0.37
MutPred		0.64		Gain of methylation at T74 (P = 0.0206)
MVP		0.20
MPC		2.1
ClinPred		0.56	D
GERP RS		1.9
PromoterAI		0.034	Neutral
Varity_R		0.16
gMVP		0.83
Mutation Taster		=80/20	polymorphism

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: rs1554675820; hg19: chr9-70972264;