Genetic Variant PABPC1:c.739-14_739-10dupTTTTT (chr8-100712798-C-CAAAAA) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002568.4(PABPC1):c.739-14_739-10dupTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000375 in 1,333,442 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000037 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PABPC1
NM_002568.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.66

Publications

0 publications found

Variant links:

Genes affected

PABPC1 (HGNC:8554): (poly(A) binding protein cytoplasmic 1) This gene encodes a poly(A) binding protein. The protein shuttles between the nucleus and cytoplasm and binds to the 3' poly(A) tail of eukaryotic messenger RNAs via RNA-recognition motifs. The binding of this protein to poly(A) promotes ribosome recruitment and translation initiation; it is also required for poly(A) shortening which is the first step in mRNA decay. The gene is part of a small gene family including three protein-coding genes and several pseudogenes.[provided by RefSeq, Aug 2010]

PABPC1 links:

ENSG00000310385 (HGNC:):

ENSG00000310385 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002568.4. 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
	PABPC1	NM_002568.4	MANE Select	c.739-14_739-10dupTTTTT		intron	N/A	NP_002559.2
	PABPC1	NM_001438282.1		c.739-14_739-10dupTTTTT		intron	N/A	NP_001425211.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PABPC1	ENST00000318607.10	TSL:1 MANE Select	c.739-14_739-10dupTTTTT	intron	N/A	ENSP00000313007.5	P11940-1
PABPC1	ENST00000610907.2	TSL:1	c.595-14_595-10dupTTTTT	intron	N/A	ENSP00000478108.2	A0A087WTT1
PABPC1	ENST00000900770.1		c.832-14_832-10dupTTTTT	intron	N/A	ENSP00000570829.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

121690

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000375

AC:

AN:

1333442

Hom.:

Cov.:

AF XY:

0.00000455

AC XY:

AN XY:

658846

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

28330

American (AMR)

AF:

0.00

AC:

AN:

25978

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21622

East Asian (EAS)

AF:

0.00

AC:

AN:

36494

South Asian (SAS)

AF:

0.0000434

AC:

AN:

69132

European-Finnish (FIN)

AF:

0.0000207

AC:

AN:

48234

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5120

European-Non Finnish (NFE)

AF:

9.58e-7

AC:

AN:

1043942

Other (OTH)

AF:

0.00

AC:

AN:

54590

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000642403), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.305

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

121690

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

58852

African (AFR)

AF:

0.00

AC:

AN:

27736

American (AMR)

AF:

0.00

AC:

AN:

13108

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3068

East Asian (EAS)

AF:

0.00

AC:

AN:

4568

South Asian (SAS)

AF:

0.00

AC:

AN:

3906

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7324

Middle Eastern (MID)

AF:

0.00

AC:

AN:

260

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

59208

Other (OTH)

AF:

0.00

AC:

AN:

1730

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.7

Splicing

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

Publications

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8-100712798-CAAAAAA-CAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over