rs372134430

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-55902092-C-T
• chr12-55902092-C-A
• chr12-55902092-C-G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_032345.3(PYM1):​c.395G>A​(p.Arg132Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: PYM1 NM_032345.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.026678264).
• BS2: High AC in GnomAdExome4 at 15 AD gene.

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>A	p.Arg132Gln	missense	Exon 3 of 3	NP_115721.1	Q9BRP8-1
	PYM1	NM_001143853.1		c.392G>A	p.Arg131Gln	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>A	p.Arg132Gln	missense	Exon 3 of 3	ENSP00000386156.2	Q9BRP8-1
	PYM1	ENST00000398213.4	TSL:2	c.392G>A	p.Arg131Gln	missense	Exon 3 of 3	ENSP00000381271.4	Q9BRP8-2
	PYM1	ENST00000859965.1		c.302G>A	p.Arg101Gln	missense	Exon 3 of 3	ENSP00000530024.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152086 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000801 AC: 2 AN: 249538 AF XY: 0.00000739

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461880 Hom.: 0 Cov.: 35 AF XY: 0.0000124 AC XY: 9 AN XY: 727240

African (AFR) AF: 0.0000299 AC: 1 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: 0.0000126 AC: 14 AN: 1112012

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

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152086 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74278

African (AFR) AF: 0.0000241 AC: 1 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000101 Hom.: 0

Bravo AF: 0.0000264

ESP6500AA AF: 0.000254 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.058
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.86
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-0.98	T
PhyloP100		1.2
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.50	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	0.74	T
Polyphen		0.0	B
Vest4		0.093
MVP		0.068
MPC		0.84
ClinPred		0.052	T
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.015
gMVP		0.11
Mutation Taster		=94/6	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;