chr8-100704305-G-C

Variant names:

• chr8-100704305-G-C
• NM_002568.4:c.1904C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002568.4(PABPC1):​c.1904C>G​(p.Thr635Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PABPC1 NM_002568.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.09

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12241033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PABPC1	NM_002568.4	c.1904C>G	p.Thr635Ser	missense_variant	Exon 14 of 15	ENST00000318607.10	NP_002559.2
PABPC1	XM_005250861.4	c.1904C>G	p.Thr635Ser	missense_variant	Exon 14 of 15		XP_005250918.1
PABPC1	XM_047421694.1	c.1904C>G	p.Thr635Ser	missense_variant	Exon 14 of 14		XP_047277650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PABPC1	ENST00000318607.10	c.1904C>G	p.Thr635Ser	missense_variant	Exon 14 of 15	1	NM_002568.4	ENSP00000313007.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460532 Hom.: 0 Cov.: 29 AF XY: 0.00000275 AC XY: 2 AN XY: 726670

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.073	T;T;T;T;T;T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.014
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.66	T;T;T;T;T;T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.12	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.80	N;.;.;.;.;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.11	N;N;N;N;N;.
REVEL	Benign	0.071
Sift	Benign	0.21	T;T;T;T;T;.
Sift4G	Benign	0.32	T;T;T;T;T;T
Polyphen		0.0	B;.;B;.;.;.
Vest4		0.12
MutPred		0.087		Loss of glycosylation at T635 (P = 0.0735);.;.;.;.;.;
MVP		0.33
MPC		0.015
ClinPred		0.41	T
GERP RS		5.5
Varity_R		0.15
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: chr8-101716533;