8-100712798-CA-CAAAA

Variant names:

• chr8-100712798-C-CAAA
• rs34574721
• NM_002568.4:c.739-12_739-10dupTTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002568.4(PABPC1):​c.739-12_739-10dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000334 in 1,453,806 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000049 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00036 (0 hom.)
• Consequence: PABPC1 NM_002568.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66

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_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PABPC1	NM_002568.4	c.739-12_739-10dupTTT		intron_variant	Intron 5 of 14	ENST00000318607.10	NP_002559.2
PABPC1	XM_005250861.4	c.739-12_739-10dupTTT		intron_variant	Intron 5 of 14		XP_005250918.1
PABPC1	XM_047421694.1	c.739-12_739-10dupTTT		intron_variant	Intron 5 of 13		XP_047277650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PABPC1	ENST00000318607.10	c.739-12_739-10dupTTT		intron_variant	Intron 5 of 14	1	NM_002568.4	ENSP00000313007.5

Frequencies

GnomAD3 genomes AF: 0.0000493 AC: 6 AN: 121666 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000361

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000845

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00287 AC: 339 AN: 118300 Hom.: 0 AF XY: 0.00315 AC XY: 205 AN XY: 65134

Gnomad AFR exome AF: 0.00513

Gnomad AMR exome AF: 0.00126

Gnomad ASJ exome AF: 0.00358

Gnomad EAS exome AF: 0.00182

Gnomad SAS exome AF: 0.00608

Gnomad FIN exome AF: 0.00415

Gnomad NFE exome AF: 0.00201

Gnomad OTH exome AF: 0.00430

GnomAD4 exome AF: 0.000360 AC: 480 AN: 1332092 Hom.: 0 Cov.: 31 AF XY: 0.000463 AC XY: 305 AN XY: 658056

Gnomad4 AFR exome AF: 0.000565

Gnomad4 AMR exome AF: 0.000618

Gnomad4 ASJ exome AF: 0.000741

Gnomad4 EAS exome AF: 0.000384

Gnomad4 SAS exome AF: 0.00186

Gnomad4 FIN exome AF: 0.00179

Gnomad4 NFE exome AF: 0.000175

Gnomad4 OTH exome AF: 0.000330

GnomAD4 genome AF: 0.0000493 AC: 6 AN: 121714 Hom.: 0 Cov.: 29 AF XY: 0.0000170 AC XY: 1 AN XY: 58900

Gnomad4 AFR AF: 0.0000360

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000845

Gnomad4 OTH AF: 0.00

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

LitVar

Other links and lift over

dbSNP: rs34574721; hg19: chr8-101725026;