chr8-100703359-T-TTTTAAACAGTTGGAACACCGGTGG

Variant names:

• chr8-100703359-T-TTTTAAACAGTTGGAACACCGGTGG
• NM_002568.4:c.*2-1_*2insCCACCGGTGTTCCAACTGTTTAAA

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_002568.4(PABPC1):​c.*2-1_*2insCCACCGGTGTTCCAACTGTTTAAA variant causes a splice acceptor, intron change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: PABPC1 NM_002568.4 splice_acceptor, intron
• Clinical Significance: Not reported in ClinVar
• 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 Likely_pathogenic. Variant got 6 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.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PABPC1	NM_002568.4	c.*2-1_*2insCCACCGGTGTTCCAACTGTTTAAA		splice_acceptor_variant, intron_variant	Intron 14 of 14	ENST00000318607.10	NP_002559.2
PABPC1	XM_047421694.1	c.*938_*939insCCACCGGTGTTCCAACTGTTTAAA		3_prime_UTR_variant	Exon 14 of 14		XP_047277650.1
PABPC1	XM_005250861.4	c.*19-1_*19insCCACCGGTGTTCCAACTGTTTAAA		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_*2insCCACCGGTGTTCCAACTGTTTAAA		splice_acceptor_variant, intron_variant	Intron 14 of 14	1	NM_002568.4	ENSP00000313007.5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-101715587;