8-100712798-CAAAAAA-CAAAAAAAAA

Variant names:

• chr8-100712798-C-CAAA
• rs34574721
• NM_002568.4:c.739-12_739-10dupTTT

Variant summary

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

The NM_002568.4(PABPC1):​c.739-12_739-10dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000334 in 1,453,806 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.000049 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00036 (0 hom.)
• Consequence: PABPC1 NM_002568.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66
• Publications: 2 publications found

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]

ENSG00000310385 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.739-12_739-10dupTTT		intron	N/A	NP_002559.2
	PABPC1	NM_001438282.1		c.739-12_739-10dupTTT		intron	N/A	NP_001425211.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PABPC1	ENST00000318607.10	TSL:1 MANE Select	c.739-12_739-10dupTTT		intron	N/A	ENSP00000313007.5	P11940-1
	PABPC1	ENST00000610907.2	TSL:1	c.595-12_595-10dupTTT		intron	N/A	ENSP00000478108.2	A0A087WTT1
	PABPC1	ENST00000900770.1		c.832-12_832-10dupTTT		intron	N/A	ENSP00000570829.1

Frequencies

GnomAD3 genomes AF: 0.0000493 AC: 6 AN: 121666 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000361

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: 0.0000845

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00287 AC: 339 AN: 118300 AF XY: 0.00315

Gnomad AFR exome AF: 0.00513

Gnomad AMR exome AF: 0.00126

Gnomad ASJ exome AF: 0.00358

Gnomad EAS exome AF: 0.00182

Gnomad FIN exome AF: 0.00415

Gnomad NFE exome AF: 0.00201

Gnomad OTH exome AF: 0.00430

GnomAD4 exome AF: 0.000360 AC: 480 AN: 1332092 Hom.: 0 Cov.: 31 AF XY: 0.000463 AC XY: 305 AN XY: 658056

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

African (AFR) AF: 0.000565 AC: 16 AN: 28296

American (AMR) AF: 0.000618 AC: 16 AN: 25884

Ashkenazi Jewish (ASJ) AF: 0.000741 AC: 16 AN: 21590

East Asian (EAS) AF: 0.000384 AC: 14 AN: 36452

South Asian (SAS) AF: 0.00186 AC: 128 AN: 68894

European-Finnish (FIN) AF: 0.00179 AC: 86 AN: 47978

Middle Eastern (MID) AF: 0.000587 AC: 3 AN: 5114

European-Non Finnish (NFE) AF: 0.000175 AC: 183 AN: 1043342

Other (OTH) AF: 0.000330 AC: 18 AN: 54542

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000493 AC: 6 AN: 121714 Hom.: 0 Cov.: 29 AF XY: 0.0000170 AC XY: 1 AN XY: 58900

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

African (AFR) AF: 0.0000360 AC: 1 AN: 27796

American (AMR) AF: 0.00 AC: 0 AN: 13126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3068

East Asian (EAS) AF: 0.00 AC: 0 AN: 4554

South Asian (SAS) AF: 0.00 AC: 0 AN: 3890

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 244

European-Non Finnish (NFE) AF: 0.0000845 AC: 5 AN: 59188

Other (OTH) AF: 0.00 AC: 0 AN: 1748

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000433 Hom.: 75

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

Other links and lift over

dbSNP: rs34574721; hg19: chr8-101725026;