NM_032345.3:c.230A>G

Variant names:

• chr12-55902257-T-C
• NM_032345.3:c.230A>G

Variant summary

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

The NM_032345.3(PYM1):​c.230A>G​(p.Glu77Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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)
• Consequence: PYM1 NM_032345.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.43
• Publications: 0 publications found

Genes affected

PYM1 (HGNC:30258): (PYM homolog 1, exon junction complex associated factor) Enables ribosome binding activity. Involved in exon-exon junction complex disassembly; nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; and positive regulation of translation. Located in cell junction; cytosol; and nuclear lumen. Part of exon-exon junction complex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.17213207).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032345.3. 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
	PYM1	NM_032345.3	MANE Select	c.230A>G	p.Glu77Gly	missense	Exon 3 of 3	NP_115721.1	Q9BRP8-1
	PYM1	NM_001143853.1		c.227A>G	p.Glu76Gly	missense	Exon 3 of 3	NP_001137325.1	Q9BRP8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PYM1	ENST00000408946.7	TSL:1 MANE Select	c.230A>G	p.Glu77Gly	missense	Exon 3 of 3	ENSP00000386156.2	Q9BRP8-1
	PYM1	ENST00000398213.4	TSL:2	c.227A>G	p.Glu76Gly	missense	Exon 3 of 3	ENSP00000381271.4	Q9BRP8-2
	PYM1	ENST00000859965.1		c.137A>G	p.Glu46Gly	missense	Exon 3 of 3	ENSP00000530024.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

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	0.087
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.070	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.4
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.064
Sift	Benign	0.071	T
Sift4G	Benign	0.15	T
Polyphen		0.95	P
Vest4		0.16
MutPred		0.18		Loss of solvent accessibility (P = 0.0387)
MVP		0.14
MPC		1.3
ClinPred		0.83	D
GERP RS		5.3
Varity_R		0.13
gMVP		0.36
Mutation Taster		=70/30	polymorphism

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

hg19: chr12-56296041;