rs6031869

Positions:

• chr20-44932595-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001372179.1(PABPC1L):​c.1330+163C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 595,820 control chromosomes in the GnomAD database, including 4,535 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (2118 hom., cov: 32)
  • Exomes 𝑓: 0.095 (2417 hom.)
• Consequence: PABPC1L NM_001372179.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247

Genes affected

PABPC1L (HGNC:15797): (poly(A) binding protein cytoplasmic 1 like) This gene belongs to the polyadenylate-binding protein type-1 family of proteins. Members of this family bind to the polyA tails of mRNAs to regulate mRNA stability and translation. The mouse ortholog of this gene is required for female fertility. In human, expression of a functional protein is regulated by alternative splicing. The protein-coding splice variant for this gene is abundantly expressed in human oocytes, while a noncoding splice variant subject to nonsense-mediated decay is the predominant splice variant expressed in somatic tissues. [provided by RefSeq, Aug 2019]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PABPC1L	NM_001372179.1	c.1330+163C>T		intron_variant		ENST00000217073.7	NP_001359108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PABPC1L	ENST00000217073.7	c.1330+163C>T		intron_variant		5	NM_001372179.1	ENSP00000217073	P4

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21776 AN: 152008 Hom.: 2111 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.0593

Gnomad AMR AF: 0.0897

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.0364

Gnomad FIN AF: 0.0934

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.0913

Gnomad OTH AF: 0.135

GnomAD4 exome AF: 0.0952 AC: 42241 AN: 443694 Hom.: 2417 Cov.: 6 AF XY: 0.0917 AC XY: 21157 AN XY: 230650

Gnomad4 AFR exome AF: 0.266

Gnomad4 AMR exome AF: 0.0762

Gnomad4 ASJ exome AF: 0.108

Gnomad4 EAS exome AF: 0.139

Gnomad4 SAS exome AF: 0.0397

Gnomad4 FIN exome AF: 0.0897

Gnomad4 NFE exome AF: 0.0909

Gnomad4 OTH exome AF: 0.108

GnomAD4 genome AF: 0.143 AC: 21812 AN: 152126 Hom.: 2118 Cov.: 32 AF XY: 0.141 AC XY: 10452 AN XY: 74384

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.0897

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.0367

Gnomad4 FIN AF: 0.0934

Gnomad4 NFE AF: 0.0913

Gnomad4 OTH AF: 0.136

Alfa AF: 0.120 Hom.: 226

Bravo AF: 0.153

Asia WGS AF: 0.0870 AC: 305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.8
DANN	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6031869; hg19: chr20-43561236; COSMIC: COSV53840124; COSMIC: COSV53840124;