Variant 14-23321471-TGGC-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PS1_Moderate

The NM_004643.4(PABPN1):c.21_23del(p.Ala11?) variant causes a start lost, inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000651 in 1,152,136 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00071 ( 0 hom. )

Consequence

PABPN1
NM_004643.4 start_lost, inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.81

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]

PABPN1 links:

BCL2L2-PABPN1 (HGNC:):

BCL2L2-PABPN1 links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1

Start lost variant, no new inframe start found.

PS1

Another start lost variant in NM_004643.4 (PABPN1) was described as [Pathogenic] in Lovd

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PABPN1	NM_004643.4 linkuse as main transcript	c.21_23del	p.Ala11?	start_lost, inframe_deletion	1/7	ENST00000216727.9	NP_004634.1
BCL2L2-PABPN1	NM_001387343.1 linkuse as main transcript	c.529-691_529-689del		intron_variant			NP_001374272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PABPN1	ENST00000216727.9 linkuse as main transcript	c.21_23del	p.Ala11?	start_lost, inframe_deletion	1/7	1	NM_004643.4	ENSP00000216727	P1	Q86U42-1
PABPN1	ENST00000397276.6 linkuse as main transcript	c.21_23del	p.Ala11?	start_lost, inframe_deletion	1/6	1		ENSP00000380446		Q86U42-2

Frequencies

GnomAD3 genomes

AF:

0.000259

AC:

AN:

150628

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000198

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000489

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00120

AC:

AN:

7496

Hom.:

AF XY:

0.00126

AC XY:

AN XY:

3956

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0152

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00153

Gnomad NFE exome

AF:

0.000781

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000710

AC:

711

AN:

1001398

Hom.:

AF XY:

0.000738

AC XY:

350

AN XY:

474352

show subpopulations

Gnomad4 AFR exome

AF:

0.000553

Gnomad4 AMR exome

AF:

0.00175

Gnomad4 ASJ exome

AF:

0.000475

Gnomad4 EAS exome

AF:

0.00229

Gnomad4 SAS exome

AF:

0.000212

Gnomad4 FIN exome

AF:

0.00213

Gnomad4 NFE exome

AF:

0.000652

Gnomad4 OTH exome

AF:

0.000932

GnomAD4 genome

AF:

0.000259

AC:

AN:

150738

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

73640

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.000198

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000489

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Oculopharyngeal muscular dystrophy

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Sep 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over