13-28138919-C-T

Variant names:

• chr13-28138919-C-T
• rs1869179334
• NM_175854.8:c.262C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_175854.8(PAN3):​c.262C>T​(p.Leu88Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000825 in 1,211,738 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: not found (cov: 30)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: PAN3 NM_175854.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• Publications: 0 publications found

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]

PAN3-AS1 (HGNC:39932): (PAN3 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=1.15 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175854.8. 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
	PAN3	NM_175854.8	MANE Select	c.262C>T	p.Leu88Leu	synonymous	Exon 1 of 19	NP_787050.6
	PAN3-AS1	NR_029383.1		n.256G>A		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAN3	ENST00000380958.8	TSL:5 MANE Select	c.262C>T	p.Leu88Leu	synonymous	Exon 1 of 19	ENSP00000370345.3	Q58A45-1
	PAN3	ENST00000913194.1		c.262C>T	p.Leu88Leu	synonymous	Exon 1 of 18	ENSP00000583253.1
	PAN3	ENST00000503791.5	TSL:2	n.414C>T		non_coding_transcript_exon	Exon 1 of 14

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 8.25e-7 AC: 1 AN: 1211738 Hom.: 0 Cov.: 33 AF XY: 0.00000170 AC XY: 1 AN XY: 588052

African (AFR) AF: 0.00 AC: 0 AN: 24890

American (AMR) AF: 0.00 AC: 0 AN: 16074

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16832

East Asian (EAS) AF: 0.00 AC: 0 AN: 29412

South Asian (SAS) AF: 0.00 AC: 0 AN: 47918

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29802

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4884

European-Non Finnish (NFE) AF: 0.00000101 AC: 1 AN: 992742

Other (OTH) AF: 0.00 AC: 0 AN: 49184

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Benign	0.96
PhyloP100		1.2
PromoterAI		0.026	Neutral

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: rs1869179334; hg19: chr13-28713056;