14-23321490-G-GGCAGCA
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS2_Supporting
The NM_004643.4(PABPN1):c.27_32dupAGCAGC(p.Ala10_Ala11dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000501 in 1,198,112 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
PABPN1
NM_004643.4 disruptive_inframe_insertion
NM_004643.4 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.57
Publications
0 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 -1 ACMG points.
BS2
High AC in GnomAdExome4 at 5 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PABPN1 | ENST00000216727.9 | c.27_32dupAGCAGC | p.Ala10_Ala11dup | disruptive_inframe_insertion | Exon 1 of 7 | 1 | NM_004643.4 | ENSP00000216727.4 | ||
BCL2L2-PABPN1 | ENST00000553781.5 | c.433-685_433-680dupAGCAGC | intron_variant | Intron 3 of 8 | 2 | ENSP00000451320.1 |
Frequencies
GnomAD3 genomes AF: 0.00000663 AC: 1AN: 150828Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
150828
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: 0.00000477 AC: 5AN: 1047284Hom.: 0 Cov.: 31 AF XY: 0.0000101 AC XY: 5AN XY: 497094 show subpopulations
GnomAD4 exome
AF:
AC:
5
AN:
1047284
Hom.:
Cov.:
31
AF XY:
AC XY:
5
AN XY:
497094
show subpopulations
African (AFR)
AF:
AC:
0
AN:
21354
American (AMR)
AF:
AC:
0
AN:
7034
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
12336
East Asian (EAS)
AF:
AC:
0
AN:
22638
South Asian (SAS)
AF:
AC:
0
AN:
19364
European-Finnish (FIN)
AF:
AC:
0
AN:
23230
Middle Eastern (MID)
AF:
AC:
0
AN:
2728
European-Non Finnish (NFE)
AF:
AC:
5
AN:
898012
Other (OTH)
AF:
AC:
0
AN:
40588
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.485
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome AF: 0.00000663 AC: 1AN: 150828Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 73640 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
150828
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
73640
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41274
American (AMR)
AF:
AC:
0
AN:
15136
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3460
East Asian (EAS)
AF:
AC:
0
AN:
5176
South Asian (SAS)
AF:
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
AC:
0
AN:
10050
Middle Eastern (MID)
AF:
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67608
Other (OTH)
AF:
AC:
0
AN:
2070
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
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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