chr13-28138680-C-T

Variant names:

• chr13-28138680-C-T
• rs1869125353
• NM_175854.8:c.23C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_175854.8(PAN3):​c.23C>T​(p.Pro8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000004 in 750,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000040 (0 hom.)
• Consequence: PAN3 NM_175854.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.597
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18661314).

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.23C>T	p.Pro8Leu	missense	Exon 1 of 19	NP_787050.6
	PAN3-AS1	NR_029383.1		n.495G>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.23C>T	p.Pro8Leu	missense	Exon 1 of 19	ENSP00000370345.3	Q58A45-1
	PAN3	ENST00000913194.1		c.23C>T	p.Pro8Leu	missense	Exon 1 of 18	ENSP00000583253.1
	PAN3	ENST00000503791.5	TSL:2	n.175C>T		non_coding_transcript_exon	Exon 1 of 14

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000400 AC: 3 AN: 750798 Hom.: 0 Cov.: 10 AF XY: 0.00000267 AC XY: 1 AN XY: 374554

African (AFR) AF: 0.00 AC: 0 AN: 15028

American (AMR) AF: 0.00 AC: 0 AN: 8164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13094

East Asian (EAS) AF: 0.00 AC: 0 AN: 25064

South Asian (SAS) AF: 0.0000608 AC: 2 AN: 32882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25868

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3616

European-Non Finnish (NFE) AF: 0.00000168 AC: 1 AN: 593706

Other (OTH) AF: 0.00 AC: 0 AN: 33376

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.15
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.85	T
M_CAP	Pathogenic	0.80	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.60
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.010	D
Vest4		0.20
MutPred		0.10		Loss of glycosylation at P8 (P = 0.0301)
MVP		0.36
MPC		1.8
ClinPred		0.50	T
GERP RS		2.6
PromoterAI		-0.037	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.28
Mutation Taster		=92/8	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: rs1869125353; hg19: chr13-28712817;