14-23321471-TGGCGGCGGCGGCGGC-TGGCGGC
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP3BS2_Supporting
The NM_004643.4(PABPN1):c.15_23delGGCGGCGGC(p.Ala6_Ala8del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000104 in 1,155,608 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
PABPN1
NM_004643.4 disruptive_inframe_deletion
NM_004643.4 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.49
Publications
1 publications found
Genes affected
PABPN1 (HGNC:8565): (poly(A) binding protein nuclear 1) This gene encodes an abundant nuclear protein that binds with high affinity to nascent poly(A) tails. The protein is required for progressive and efficient polymerization of poly(A) tails at the 3' ends of eukaryotic transcripts and controls the size of the poly(A) tail to about 250 nt. At steady-state, this protein is localized in the nucleus whereas a different poly(A) binding protein is localized in the cytoplasm. This gene contains a GCG trinucleotide repeat at the 5' end of the coding region, and expansion of this repeat from the normal 6 copies to 8-13 copies leads to autosomal dominant oculopharyngeal muscular dystrophy (OPMD) disease. Related pseudogenes have been identified on chromosomes 19 and X. Read-through transcription also exists between this gene and the neighboring upstream BCL2-like 2 (BCL2L2) gene. [provided by RefSeq, Dec 2010]
BCL2L2-PABPN1 (HGNC:42959): (BCL2L2-PABPN1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring BCL2L2 (BCL2-like 2) and PABPN1 (poly(A) binding protein, nuclear 1) genes on chromosome 14. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Dec 2010]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
BP3
Nonframeshift variant in repetitive region in NM_004643.4
BS2
High AC in GnomAdExome4 at 10 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_004643.4. 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 |
|---|---|---|---|---|---|---|---|---|---|
| PABPN1 | MANE Select | c.15_23delGGCGGCGGC | p.Ala6_Ala8del | disruptive_inframe_deletion | Exon 1 of 7 | NP_004634.1 | Q86U42-1 | ||
| PABPN1 | c.15_23delGGCGGCGGC | p.Ala6_Ala8del | disruptive_inframe_deletion | Exon 1 of 6 | NP_001347480.1 | Q86U42-2 | |||
| BCL2L2-PABPN1 | c.550-697_550-689delGGCGGCGGC | intron | N/A | NP_001374269.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PABPN1 | TSL:1 MANE Select | c.15_23delGGCGGCGGC | p.Ala6_Ala8del | disruptive_inframe_deletion | Exon 1 of 7 | ENSP00000216727.4 | Q86U42-1 | ||
| PABPN1 | TSL:1 | c.15_23delGGCGGCGGC | p.Ala6_Ala8del | disruptive_inframe_deletion | Exon 1 of 6 | ENSP00000380446.2 | Q86U42-2 | ||
| BCL2L2-PABPN1 | TSL:2 | c.433-697_433-689delGGCGGCGGC | intron | N/A | ENSP00000451320.1 | Q92843-2 |
Frequencies
GnomAD3 genomes 0.0000133 AC: 2AN: 150644Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
150644
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000995 AC: 10AN: 1004964Hom.: 0 AF XY: 0.00000840 AC XY: 4AN XY: 476176 show subpopulations
GnomAD4 exome
AF:
AC:
10
AN:
1004964
Hom.:
AF XY:
AC XY:
4
AN XY:
476176
show subpopulations
African (AFR)
AF:
AC:
0
AN:
19972
American (AMR)
AF:
AC:
0
AN:
5794
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
10612
East Asian (EAS)
AF:
AC:
0
AN:
17698
South Asian (SAS)
AF:
AC:
0
AN:
18946
European-Finnish (FIN)
AF:
AC:
0
AN:
18114
Middle Eastern (MID)
AF:
AC:
0
AN:
2592
European-Non Finnish (NFE)
AF:
AC:
10
AN:
873482
Other (OTH)
AF:
AC:
0
AN:
37754
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.540
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<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 0.0000133 AC: 2AN: 150644Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1AN XY: 73536 show subpopulations
GnomAD4 genome
AF:
AC:
2
AN:
150644
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
73536
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41178
American (AMR)
AF:
AC:
0
AN:
15150
Ashkenazi Jewish (ASJ)
AF:
AC:
1
AN:
3456
East Asian (EAS)
AF:
AC:
0
AN:
5138
South Asian (SAS)
AF:
AC:
0
AN:
4790
European-Finnish (FIN)
AF:
AC:
0
AN:
10110
Middle Eastern (MID)
AF:
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67522
Other (OTH)
AF:
AC:
0
AN:
2076
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.625
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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