chrX-91436592-C-A

Position:

• chrX-91436592-C-A

Variant summary

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

The NM_080832.3(PABPC5):​c.1015C>A​(p.Gln339Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: PABPC5 NM_080832.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.82

Genes affected

PABPC5 (HGNC:13629): (poly(A) binding protein cytoplasmic 5) This gene encodes a protein that binds to the polyA tail found at the 3' end of most eukaryotic mRNAs. It is thought to play a role in the regulation of mRNA metabolic processes in the cytoplasm. This gene is located in a gene-poor region within the X-specific 13d-sY43 subinterval of the chromosome Xq21.3/Yp11.2 homology block. It is located close to translocation breakpoints associated with premature ovarian failure, and is therefore a potential candidate gene for this disorder. [provided by RefSeq, May 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=0.16192272).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PABPC5	NM_080832.3	c.1015C>A	p.Gln339Lys	missense_variant	2/2	ENST00000312600.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PABPC5	ENST00000312600.4	c.1015C>A	p.Gln339Lys	missense_variant	2/2	1	NM_080832.3	P1
PABPC5	ENST00000373105.1	c.523C>A	p.Gln175Lys	missense_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 16, 2021

The c.1015C>A (p.Q339K) alteration is located in exon 2 (coding exon 1) of the PABPC5 gene. This alteration results from a C to A substitution at nucleotide position 1015, causing the glutamine (Q) at amino acid position 339 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	22
DANN	Benign	0.86
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	0.90	D;D
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.17	N;N
REVEL	Benign	0.086
Sift	Benign	0.39	T;T
Sift4G	Benign	0.59	T;T
Polyphen		0.51	.;P
Vest4		0.18
MutPred		0.41		.;Gain of methylation at Q339 (P = 0.0175);
MVP		0.39
MPC		1.2
ClinPred		0.68	D
GERP RS		4.1
Varity_R		0.37
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: chrX-90691591;