12-55922040-G-A

Variant names:

• chr12-55922040-G-A
• rs772704
• NM_032345.3:c.37+5685C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032345.3(PYM1):​c.37+5685C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 151,534 control chromosomes in the GnomAD database, including 53,855 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.84 (53855 hom., cov: 28)
• Consequence: PYM1 NM_032345.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 3 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]

LOC124902941 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

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.37+5685C>T		intron	N/A	NP_115721.1	Q9BRP8-1
	PYM1	NM_001143853.1		c.34+5036C>T		intron	N/A	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.37+5685C>T		intron	N/A	ENSP00000386156.2	Q9BRP8-1
	PYM1	ENST00000398213.4	TSL:2	c.34+5036C>T		intron	N/A	ENSP00000381271.4	Q9BRP8-2
	PYM1	ENST00000859965.1		c.37+5685C>T		intron	N/A	ENSP00000530024.1

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127342 AN: 151418 Hom.: 53817 Cov.: 28

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.900

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.900

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.811

Gnomad OTH AF: 0.842

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.841 AC: 127439 AN: 151534 Hom.: 53855 Cov.: 28 AF XY: 0.838 AC XY: 61995 AN XY: 73992

African (AFR) AF: 0.928 AC: 38439 AN: 41402

American (AMR) AF: 0.788 AC: 11997 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.900 AC: 3116 AN: 3462

East Asian (EAS) AF: 0.792 AC: 4067 AN: 5138

South Asian (SAS) AF: 0.851 AC: 4086 AN: 4802

European-Finnish (FIN) AF: 0.762 AC: 7949 AN: 10434

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.811 AC: 54932 AN: 67770

Other (OTH) AF: 0.843 AC: 1771 AN: 2102

Alfa AF: 0.792 Hom.: 2051

Bravo AF: 0.840

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.57
DANN	Benign	0.24
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs772704; hg19: chr12-56315824;