chr8-100717892-G-T

Variant names:

• chr8-100717892-G-T
• rs200817756
• NM_002568.4:c.388-4C>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002568.4(PABPC1):​c.388-4C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PABPC1 NM_002568.4 splice_region, intron
• Scores: Splicing: ADA: 0.0001348
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PABPC1	NM_002568.4	c.388-4C>A		splice_region_variant, intron_variant	Intron 2 of 14	ENST00000318607.10	NP_002559.2
PABPC1	XM_005250861.4	c.388-4C>A		splice_region_variant, intron_variant	Intron 2 of 14		XP_005250918.1
PABPC1	XM_047421694.1	c.388-4C>A		splice_region_variant, intron_variant	Intron 2 of 13		XP_047277650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PABPC1	ENST00000318607.10	c.388-4C>A		splice_region_variant, intron_variant	Intron 2 of 14	1	NM_002568.4	ENSP00000313007.5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 150916 Hom.: 0 Cov.: 33 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000127 AC: 165 AN: 1303906 Hom.: 0 Cov.: 27 AF XY: 0.000152 AC XY: 98 AN XY: 643706

Gnomad4 AFR exome AF: 0.000314

Gnomad4 AMR exome AF: 0.000736

Gnomad4 ASJ exome AF: 0.0000853

Gnomad4 EAS exome AF: 0.000473

Gnomad4 SAS exome AF: 0.000338

Gnomad4 FIN exome AF: 0.000122

Gnomad4 NFE exome AF: 0.0000742

Gnomad4 OTH exome AF: 0.0000917

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000663 AC: 1 AN: 150916 Hom.: 0 Cov.: 33 AF XY: 0.0000136 AC XY: 1 AN XY: 73572

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000163 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.1
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00013
dbscSNV1_RF	Benign	0.0
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: rs200817756; hg19: chr8-101730120;