8-100712798-CAAAAAA-CAAAAAAA

Variant names:

• chr8-100712798-C-CA
• rs34574721
• NM_002568.4:c.739-10dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002568.4(PABPC1):​c.739-10dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,448,302 control chromosomes in the GnomAD database, including 12,982 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (2602 hom., cov: 29)
  • Exomes 𝑓: 0.14 (10380 hom.)
• Consequence: PABPC1 NM_002568.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 8-100712798-C-CA is Benign according to our data. Variant chr8-100712798-C-CA is described in ClinVar as Benign. ClinVar VariationId is 770194.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

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.739-10dupT		intron	N/A	NP_002559.2
	PABPC1	NM_001438282.1		c.739-10dupT		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.739-10dupT		intron	N/A	ENSP00000313007.5	P11940-1
	PABPC1	ENST00000610907.2	TSL:1	c.595-10dupT		intron	N/A	ENSP00000478108.2	A0A087WTT1
	PABPC1	ENST00000900770.1		c.832-10dupT		intron	N/A	ENSP00000570829.1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 26451 AN: 121468 Hom.: 2588 Cov.: 29

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.112

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.190

GnomAD2 exomes AF: 0.128 AC: 15099 AN: 118300 AF XY: 0.121

Gnomad AFR exome AF: 0.223

Gnomad AMR exome AF: 0.190

Gnomad ASJ exome AF: 0.0691

Gnomad EAS exome AF: 0.234

Gnomad FIN exome AF: 0.114

Gnomad NFE exome AF: 0.102

Gnomad OTH exome AF: 0.113

GnomAD4 exome AF: 0.140 AC: 185264 AN: 1326784 Hom.: 10380 Cov.: 31 AF XY: 0.139 AC XY: 90931 AN XY: 655444

African (AFR) AF: 0.222 AC: 6242 AN: 28140

American (AMR) AF: 0.221 AC: 5681 AN: 25736

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 2347 AN: 21516

East Asian (EAS) AF: 0.287 AC: 10438 AN: 36318

South Asian (SAS) AF: 0.142 AC: 9742 AN: 68530

European-Finnish (FIN) AF: 0.138 AC: 6633 AN: 47956

Middle Eastern (MID) AF: 0.145 AC: 741 AN: 5108

European-Non Finnish (NFE) AF: 0.130 AC: 135365 AN: 1039150

Other (OTH) AF: 0.149 AC: 8075 AN: 54330

GnomAD4 genome AF: 0.218 AC: 26490 AN: 121518 Hom.: 2602 Cov.: 29 AF XY: 0.224 AC XY: 13189 AN XY: 58808

African (AFR) AF: 0.336 AC: 9318 AN: 27744

American (AMR) AF: 0.286 AC: 3740 AN: 13068

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 357 AN: 3068

East Asian (EAS) AF: 0.330 AC: 1503 AN: 4548

South Asian (SAS) AF: 0.176 AC: 681 AN: 3878

European-Finnish (FIN) AF: 0.174 AC: 1269 AN: 7298

Middle Eastern (MID) AF: 0.119 AC: 29 AN: 244

European-Non Finnish (NFE) AF: 0.154 AC: 9116 AN: 59148

Other (OTH) AF: 0.192 AC: 335 AN: 1742

Alfa AF: 0.0380 Hom.: 75

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs34574721; hg19: chr8-101725026;