chr8-100712798-C-CAA

Variant names:

• chr8-100712798-C-CAA
• rs34574721
• NM_002568.4:c.739-11_739-10dupTT

Variant summary

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

The NM_002568.4(PABPC1):​c.739-11_739-10dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,451,128 control chromosomes in the GnomAD database, including 1 homozygotes. 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0022 (1 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.739-11_739-10dupTT		intron	N/A	NP_002559.2
	PABPC1	NM_001438282.1		c.739-11_739-10dupTT		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.739-11_739-10dupTT		intron	N/A	ENSP00000313007.5	P11940-1
	PABPC1	ENST00000610907.2	TSL:1	c.595-11_595-10dupTT		intron	N/A	ENSP00000478108.2	A0A087WTT1
	PABPC1	ENST00000900770.1		c.832-11_832-10dupTT		intron	N/A	ENSP00000570829.1

Frequencies

GnomAD3 genomes AF: 0.000214 AC: 26 AN: 121634 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000144

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000763

Gnomad ASJ AF: 0.000326

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000768

Gnomad FIN AF: 0.000958

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000169

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0167 AC: 1980 AN: 118300 AF XY: 0.0180

Gnomad AFR exome AF: 0.0281

Gnomad AMR exome AF: 0.0127

Gnomad ASJ exome AF: 0.0133

Gnomad EAS exome AF: 0.0153

Gnomad FIN exome AF: 0.0237

Gnomad NFE exome AF: 0.0129

Gnomad OTH exome AF: 0.0117

GnomAD4 exome AF: 0.00220 AC: 2927 AN: 1329446 Hom.: 1 Cov.: 31 AF XY: 0.00262 AC XY: 1719 AN XY: 656580

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

African (AFR) AF: 0.00361 AC: 102 AN: 28218

American (AMR) AF: 0.00933 AC: 240 AN: 25712

Ashkenazi Jewish (ASJ) AF: 0.00311 AC: 67 AN: 21554

East Asian (EAS) AF: 0.00381 AC: 138 AN: 36212

South Asian (SAS) AF: 0.00864 AC: 593 AN: 68616

European-Finnish (FIN) AF: 0.00975 AC: 465 AN: 47670

Middle Eastern (MID) AF: 0.00413 AC: 21 AN: 5090

European-Non Finnish (NFE) AF: 0.00117 AC: 1220 AN: 1041936

Other (OTH) AF: 0.00149 AC: 81 AN: 54438

⚠️ 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: 0.000214 AC: 26 AN: 121682 Hom.: 0 Cov.: 29 AF XY: 0.000255 AC XY: 15 AN XY: 58890

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

African (AFR) AF: 0.000144 AC: 4 AN: 27790

American (AMR) AF: 0.0000762 AC: 1 AN: 13124

Ashkenazi Jewish (ASJ) AF: 0.000326 AC: 1 AN: 3068

East Asian (EAS) AF: 0.00 AC: 0 AN: 4552

South Asian (SAS) AF: 0.000771 AC: 3 AN: 3890

European-Finnish (FIN) AF: 0.000958 AC: 7 AN: 7310

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

European-Non Finnish (NFE) AF: 0.000169 AC: 10 AN: 59174

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: 0.000681 Hom.: 75

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism

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; COSMIC: COSV108826428; COSMIC: COSV108826428;