GeneBe

rs193922941

Positions:

Variant summary

Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PVS1PS1_ModeratePM2PP5

The ENST00000216727.9(PABPN1):​c.9_23del​(p.AlaAlaAlaAlaAla7_?11) variant causes a start lost, inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in Lovd as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

PABPN1
ENST00000216727.9 start_lost, inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.49
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 13 ACMG points.

PVS1
Start lost variant, no new inframe start found.
PS1
Another start lost variant in ENST00000216727.9 (PABPN1) was described as [Pathogenic] in Lovd
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 14-23321471-TGGCGGCGGCGGCGGC-T is Pathogenic according to our data. Variant chr14-23321471-TGGCGGCGGCGGCGGC-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PABPN1NM_004643.4 linkuse as main transcriptc.9_23del p.AlaAlaAlaAlaAla7_?11 start_lost, inframe_deletion 1/7 ENST00000216727.9 NP_004634.1
BCL2L2-PABPN1NM_001387343.1 linkuse as main transcriptc.529-703_529-689del intron_variant NP_001374272.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PABPN1ENST00000216727.9 linkuse as main transcriptc.9_23del p.AlaAlaAlaAlaAla7_?11 start_lost, inframe_deletion 1/71 NM_004643.4 ENSP00000216727 P1Q86U42-1
PABPN1ENST00000397276.6 linkuse as main transcriptc.9_23del p.AlaAlaAlaAlaAla7_?11 start_lost, inframe_deletion 1/61 ENSP00000380446 Q86U42-2

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs193922941; hg19: chr14-23790680; API