rs57799615

Variant names:

• chr8-100709528-A-C
• rs57799615
• NM_002568.4:c.1176T>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_002568.4(PABPC1):​c.1176T>G​(p.Val392Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0674 in 131,260 control chromosomes in the GnomAD database, including 623 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.067 (623 hom., cov: 33)
  • Exomes 𝑓: 0.11 (533 hom.)
  • Failed GnomAD Quality Control
• Consequence: PABPC1 NM_002568.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.967

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 8-100709528-A-C is Benign according to our data. Variant chr8-100709528-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3356114.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.967 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PABPC1	NM_002568.4	c.1176T>G	p.Val392Val	synonymous_variant	Exon 8 of 15	ENST00000318607.10	NP_002559.2
PABPC1	XM_005250861.4	c.1176T>G	p.Val392Val	synonymous_variant	Exon 8 of 15		XP_005250918.1
PABPC1	XM_047421694.1	c.1176T>G	p.Val392Val	synonymous_variant	Exon 8 of 14		XP_047277650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PABPC1	ENST00000318607.10	c.1176T>G	p.Val392Val	synonymous_variant	Exon 8 of 15	1	NM_002568.4	ENSP00000313007.5

Frequencies

GnomAD3 genomes AF: 0.0673 AC: 8829 AN: 131166 Hom.: 617 Cov.: 33

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0379

Gnomad ASJ AF: 0.00594

Gnomad EAS AF: 0.0158

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.0116

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.0569

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.105 AC: 90984 AN: 864356 Hom.: 533 Cov.: 60 AF XY: 0.113 AC XY: 49318 AN XY: 434880

Gnomad4 AFR exome AF: 0.331

Gnomad4 AMR exome AF: 0.220

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.0679

Gnomad4 SAS exome AF: 0.180

Gnomad4 FIN exome AF: 0.108

Gnomad4 NFE exome AF: 0.0858

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.0674 AC: 8848 AN: 131260 Hom.: 623 Cov.: 33 AF XY: 0.0679 AC XY: 4308 AN XY: 63406

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.0379

Gnomad4 ASJ AF: 0.00594

Gnomad4 EAS AF: 0.0156

Gnomad4 SAS AF: 0.0142

Gnomad4 FIN AF: 0.0116

Gnomad4 NFE AF: 0.0109

Gnomad4 OTH AF: 0.0580

Alfa AF: 0.303 Hom.: 37

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

PABPC1-related condition Benign:1

Sep 16, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	11
DANN	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs57799615; hg19: chr8-101721756; COSMIC: COSV59400338; COSMIC: COSV59400338;