dbSNP rs9508005: PAN3:c.853-4574T>G (chr13-28215657-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0400

Publications

1 publications found

Variant links:

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 links:

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

EEF1A1P3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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.853-4574T>G		intron	N/A	NP_787050.6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PAN3	ENST00000380958.8	TSL:5 MANE Select	c.853-4574T>G	intron	N/A	ENSP00000370345.3	Q58A45-1
PAN3	ENST00000913194.1		c.691-4574T>G	intron	N/A	ENSP00000583253.1
PAN3	ENST00000399613.1	TSL:5	c.253-4574T>G	intron	N/A	ENSP00000382522.1	A0A0C4DFZ9

Frequencies

GnomAD3 genomes

AF:

0.0637

AC:

9699

AN:

152216

Hom.:

425

Cov.:

show subpopulations

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.:

AF XY:

0.0854

AC XY:

53302

AN XY:

624392

show subpopulations

African (AFR)

AF:

0.0150

AC:

430

AN:

28578

American (AMR)

AF:

0.0451

AC:

1594

AN:

35322

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

4101

AN:

24270

East Asian (EAS)

AF:

0.000114

AC:

AN:

34990

South Asian (SAS)

AF:

0.0279

AC:

2144

AN:

76730

European-Finnish (FIN)

AF:

0.0612

AC:

2564

AN:

41906

Middle Eastern (MID)

AF:

0.0991

AC:

373

AN:

3762

European-Non Finnish (NFE)

AF:

0.0974

AC:

92864

AN:

953534

Other (OTH)

AF:

0.0787

AC:

4163

AN:

52910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

4929

9858

14788

19717

24646

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3208

6416

9624

12832

16040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0637

AC:

9702

AN:

152334

Hom.:

427

Cov.:

AF XY:

0.0609

AC XY:

4536

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.0161

AC:

671

AN:

41590

American (AMR)

AF:

0.0554

AC:

847

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

603

AN:

3466

East Asian (EAS)

AF:

0.000385

AC:

AN:

5194

South Asian (SAS)

AF:

0.0265

AC:

128

AN:

4826

European-Finnish (FIN)

AF:

0.0624

AC:

662

AN:

10616

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0960

AC:

6529

AN:

68028

Other (OTH)

AF:

0.0710

AC:

150

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

482

964

1447

1929

2411

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0888

Hom.:

965

Bravo

AF:

0.0619

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.8

(source)

DANN

Benign

0.44

PhyloP100

0.040

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over