rs9508005

Positions:

• chr13-28215657-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175854.8(PAN3):​c.853-4574T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.084 in 1,404,336 control chromosomes in the GnomAD database, including 5,890 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 0.064 (427 hom., cov: 32)
  • Exomes 𝑓: 0.086 (5463 hom.)
• Consequence: PAN3 NM_175854.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400

Genes affected

PAN3 (HGNC:29991): (poly(A) specific ribonuclease subunit PAN3) Contributes to poly(A)-specific ribonuclease activity. Predicted to be involved in nuclear-transcribed mRNA poly(A) tail shortening. Predicted to act upstream of or within deadenylation-dependent decapping of nuclear-transcribed mRNA; positive regulation of cytoplasmic mRNA processing body assembly; and protein targeting. Part of PAN complex. [provided by Alliance of Genome Resources, Apr 2022]

EEF1A1P3 (HGNC:3194): (eukaryotic translation elongation factor 1 alpha 1 pseudogene 3)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.094 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAN3	NM_175854.8	c.853-4574T>G		intron_variant		ENST00000380958.8	NP_787050.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAN3	ENST00000380958.8	c.853-4574T>G		intron_variant		5	NM_175854.8	ENSP00000370345	P2
EEF1A1P3	ENST00000417549.1	n.1145T>G		non_coding_transcript_exon_variant	1/1
PAN3	ENST00000399613.1	c.253-4574T>G		intron_variant		5		ENSP00000382522	A2
PAN3	ENST00000503791.5	n.1005-4574T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0637 AC: 9699 AN: 152216 Hom.: 425 Cov.: 32

Gnomad AFR AF: 0.0162

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.0555

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0263

Gnomad FIN AF: 0.0624

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0959

Gnomad OTH AF: 0.0717

GnomAD4 exome AF: 0.0865 AC: 108237 AN: 1252002 Hom.: 5463 Cov.: 19 AF XY: 0.0854 AC XY: 53302 AN XY: 624392

Gnomad4 AFR exome AF: 0.0150

Gnomad4 AMR exome AF: 0.0451

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.000114

Gnomad4 SAS exome AF: 0.0279

Gnomad4 FIN exome AF: 0.0612

Gnomad4 NFE exome AF: 0.0974

Gnomad4 OTH exome AF: 0.0787

GnomAD4 genome AF: 0.0637 AC: 9702 AN: 152334 Hom.: 427 Cov.: 32 AF XY: 0.0609 AC XY: 4536 AN XY: 74498

Gnomad4 AFR AF: 0.0161

Gnomad4 AMR AF: 0.0554

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0265

Gnomad4 FIN AF: 0.0624

Gnomad4 NFE AF: 0.0960

Gnomad4 OTH AF: 0.0710

Alfa AF: 0.0931 Hom.: 809

Bravo AF: 0.0619

Asia WGS AF: 0.0170 AC: 59 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.8
DANN	Benign	0.44

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: rs9508005; hg19: chr13-28789794;