8-100717892-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002568.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PABPC1	NM_002568.4	MANE Select	c.388-4C>A		splice_region intron	N/A	NP_002559.2
	PABPC1	NM_001438282.1		c.388-4C>A		splice_region intron	N/A	NP_001425211.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PABPC1	ENST00000318607.10	TSL:1 MANE Select	c.388-4C>A		splice_region intron	N/A	ENSP00000313007.5	P11940-1
	PABPC1	ENST00000610907.2	TSL:1	c.244-4C>A		splice_region intron	N/A	ENSP00000478108.2	A0A087WTT1
	PABPC1	ENST00000900770.1		c.388-4C>A		splice_region intron	N/A	ENSP00000570829.1

Frequencies

GnomAD3 genomes AF: 0.00000663 AC: 1 AN: 150916 Hom.: 0 Cov.: 33

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

GnomAD2 exomes AF: 0.00 AC: 0 AN: 246164 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000314 AC: 9 AN: 28686

American (AMR) AF: 0.000736 AC: 26 AN: 35308

Ashkenazi Jewish (ASJ) AF: 0.0000853 AC: 2 AN: 23436

East Asian (EAS) AF: 0.000473 AC: 17 AN: 35908

South Asian (SAS) AF: 0.000338 AC: 25 AN: 74040

European-Finnish (FIN) AF: 0.000122 AC: 6 AN: 49042

Middle Eastern (MID) AF: 0.000187 AC: 1 AN: 5346

European-Non Finnish (NFE) AF: 0.0000742 AC: 74 AN: 997604

Other (OTH) AF: 0.0000917 AC: 5 AN: 54536

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.00 AC: 0 AN: 40988

American (AMR) AF: 0.00 AC: 0 AN: 15122

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67658

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.0000163 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.1
DANN	Benign	0.50
PhyloP100		-0.021

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

Other links and lift over

dbSNP: rs200817756; hg19: chr8-101730120;