12-55922040-G-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_032345.3(PYM1):​c.37+5685C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000218 in 151,582 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00022 (0 hom., cov: 28)
• Consequence: PYM1 NM_032345.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BS2: High AC in GnomAd4 at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYM1	NM_032345.3	c.37+5685C>A		intron_variant	Intron 1 of 2	ENST00000408946.7	NP_115721.1
PYM1	NM_001143853.1	c.34+5036C>A		intron_variant	Intron 1 of 2		NP_001137325.1
LOC124902941	XR_007063325.1	n.331+1401C>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PYM1	ENST00000408946.7	c.37+5685C>A		intron_variant	Intron 1 of 2	1	NM_032345.3	ENSP00000386156.2

Frequencies

GnomAD3 genomes AF: 0.000218 AC: 33 AN: 151466 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.000509

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000738

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000218 AC: 33 AN: 151582 Hom.: 0 Cov.: 28 AF XY: 0.000176 AC XY: 13 AN XY: 74022

Gnomad4 AFR AF: 0.000507

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00117

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000738

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.40
DANN	Benign	0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs772704; hg19: chr12-56315824;