8-100703359-T-TTTTAAACAGTTGGAACACCAGTGG

Variant names:

• chr8-100703359-T-TTTTAAACAGTTGGAACACCAGTGG
• rs1587140774
• NM_002568.4:c.*2-1_*2insCCACTGGTGTTCCAACTGTTTAAA

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_Strong

The NM_002568.4(PABPC1):​c.*2-1_*2insCCACTGGTGTTCCAACTGTTTAAA variant causes a splice acceptor, intron change. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: PABPC1 NM_002568.4 splice_acceptor, intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 6.03

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 Uncertain_significance. Variant got 4 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.23233908 fraction of the gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PABPC1	NM_002568.4	c.*2-1_*2insCCACTGGTGTTCCAACTGTTTAAA		splice_acceptor_variant, intron_variant	Intron 14 of 14	ENST00000318607.10	NP_002559.2
PABPC1	XM_047421694.1	c.*938_*939insCCACTGGTGTTCCAACTGTTTAAA		3_prime_UTR_variant	Exon 14 of 14		XP_047277650.1
PABPC1	XM_005250861.4	c.*19-1_*19insCCACTGGTGTTCCAACTGTTTAAA		splice_acceptor_variant, intron_variant	Intron 14 of 14		XP_005250918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PABPC1	ENST00000318607.10	c.*2-1_*2insCCACTGGTGTTCCAACTGTTTAAA		splice_acceptor_variant, intron_variant	Intron 14 of 14	1	NM_002568.4	ENSP00000313007.5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 48 AN: 146410 Hom.: 0 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.000405

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000405

Gnomad ASJ AF: 0.000599

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000640

Gnomad FIN AF: 0.000193

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000290

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000328 AC: 48 AN: 146518 Hom.: 0 Cov.: 30 AF XY: 0.000390 AC XY: 28 AN XY: 71762

Gnomad4 AFR AF: 0.000404

Gnomad4 AMR AF: 0.000404

Gnomad4 ASJ AF: 0.000599

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000641

Gnomad4 FIN AF: 0.000193

Gnomad4 NFE AF: 0.000290

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00662 Hom.: 0

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

CIC-rearranged sarcoma Other:1

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Children's Cancer Therapy Development Institute

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1587140774; hg19: chr8-101715587;