8-100713178-G-A

Variant names:

• chr8-100713178-G-A
• NM_002568.4:c.647C>T

Variant summary

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

The NM_002568.4(PABPC1):​c.647C>T​(p.Pro216Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000418 in 1,433,708 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: PABPC1 NM_002568.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.38

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 GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PABPC1	NM_002568.4	c.647C>T	p.Pro216Leu	missense_variant	Exon 5 of 15	ENST00000318607.10	NP_002559.2
PABPC1	XM_005250861.4	c.647C>T	p.Pro216Leu	missense_variant	Exon 5 of 15		XP_005250918.1
PABPC1	XM_047421694.1	c.647C>T	p.Pro216Leu	missense_variant	Exon 5 of 14		XP_047277650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PABPC1	ENST00000318607.10	c.647C>T	p.Pro216Leu	missense_variant	Exon 5 of 15	1	NM_002568.4	ENSP00000313007.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000418 AC: 6 AN: 1433708 Hom.: 0 Cov.: 28 AF XY: 0.00000561 AC XY: 4 AN XY: 713070

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000454

Gnomad4 OTH exome AF: 0.0000169

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.22	T;T;T;T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.79	T;T;T;T
M_CAP	Benign	0.074	D
MetaRNN	Uncertain	0.51	D;D;D;D
MetaSVM	Uncertain	0.0080	D
MutationAssessor	Benign	1.6	L;.;.;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.1	D;D;D;.
REVEL	Uncertain	0.31
Sift	Benign	0.050	D;D;D;.
Sift4G	Benign	0.13	T;T;T;T
Polyphen		0.22	B;.;B;.
Vest4		0.61
MutPred		0.53		Gain of catalytic residue at P216 (P = 0.0565);.;.;.;
MVP		0.74
MPC		1.3
ClinPred		0.96	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-101725406;