12-55902092-C-A

Variant names:

• chr12-55902092-C-A
• rs372134430
• NM_032345.3:c.395G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032345.3(PYM1):​c.395G>T​(p.Arg132Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R132Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: PYM1 NM_032345.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052908808).

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.395G>T	p.Arg132Leu	missense	Exon 3 of 3	NP_115721.1	Q9BRP8-1
	PYM1	NM_001143853.1		c.392G>T	p.Arg131Leu	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.395G>T	p.Arg132Leu	missense	Exon 3 of 3	ENSP00000386156.2	Q9BRP8-1
	PYM1	ENST00000398213.4	TSL:2	c.392G>T	p.Arg131Leu	missense	Exon 3 of 3	ENSP00000381271.4	Q9BRP8-2
	PYM1	ENST00000859965.1		c.302G>T	p.Arg101Leu	missense	Exon 3 of 3	ENSP00000530024.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461880 Hom.: 0 Cov.: 35 AF XY: 0.00000413 AC XY: 3 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.2
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.042
Sift	Benign	0.20	T
Sift4G	Benign	0.23	T
Polyphen		0.013	B
Vest4		0.16
MutPred		0.27		Gain of helix (P = 0.0496)
MVP		0.043
MPC		0.90
ClinPred		0.17	T
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.040
gMVP		0.18
Mutation Taster		=84/16	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

dbSNP: rs372134430; hg19: chr12-56295876;