X-73079229-G-C

Position:

• chrX-73079229-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_001012977.3(PABPC1L2A):​c.158C>G​(p.Pro53Arg) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 4)
• Consequence: PABPC1L2A NM_001012977.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.89

Genes affected

PABPC1L2A (HGNC:27989): (poly(A) binding protein cytoplasmic 1 like 2A) Predicted to enable RNA binding activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.75

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PABPC1L2A	NM_001012977.3	c.158C>G	p.Pro53Arg	missense_variant	1/1	ENST00000373519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PABPC1L2A	ENST00000373519.1	c.158C>G	p.Pro53Arg	missense_variant	1/1		NM_001012977.3	P1

Frequencies

GnomAD3 genomes Cov.: 4

GnomAD4 exome Cov.: 4

GnomAD4 genome Cov.: 4

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

Mar 12, 2024

The c.158C>G (p.P53R) alteration is located in exon 1 (coding exon 1) of the PABPC1L2A gene. This alteration results from a C to G substitution at nucleotide position 158, causing the proline (P) at amino acid position 53 to be replaced by an arginine (R). 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	0.29
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.099	T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.027	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-7.3	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.026	D
Sift4G	Benign	0.18	T
Vest4		0.69
MutPred		0.47		Gain of MoRF binding (P = 0.0076);
MVP		0.76
MPC		2.1
ClinPred		0.97	D
GERP RS		3.2
Varity_R		0.69
gMVP		0.54

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-72299068;