20-44912750-A-G

Position:

• chr20-44912750-A-G

Variant summary

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

The NM_001372179.1(PABPC1L):​c.284A>G​(p.Lys95Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PABPC1L NM_001372179.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.77

Genes affected

PABPC1L (HGNC:15797): (poly(A) binding protein cytoplasmic 1 like) This gene belongs to the polyadenylate-binding protein type-1 family of proteins. Members of this family bind to the polyA tails of mRNAs to regulate mRNA stability and translation. The mouse ortholog of this gene is required for female fertility. In human, expression of a functional protein is regulated by alternative splicing. The protein-coding splice variant for this gene is abundantly expressed in human oocytes, while a noncoding splice variant subject to nonsense-mediated decay is the predominant splice variant expressed in somatic tissues. [provided by RefSeq, Aug 2019]

PABPC1L (HGNC:):

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=0.18171635).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PABPC1L	NM_001372179.1	c.284A>G	p.Lys95Arg	missense_variant	2/15	ENST00000217073.7	NP_001359108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PABPC1L	ENST00000217073.7	c.284A>G	p.Lys95Arg	missense_variant	2/15	5	NM_001372179.1	ENSP00000217073.3
PABPC1L	ENST00000537323.5	n.284A>G		non_coding_transcript_exon_variant	2/14	1		ENSP00000445661.1
PABPC1L	ENST00000255136.8	c.284A>G	p.Lys95Arg	missense_variant	2/15	5		ENSP00000255136.3
PABPC1L	ENST00000217074.9	n.263A>G		non_coding_transcript_exon_variant	2/14	5		ENSP00000217074.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Sep 29, 2023

The c.284A>G (p.K95R) alteration is located in exon 2 (coding exon 2) of the PABPC1L gene. This alteration results from a A to G substitution at nucleotide position 284, causing the lysine (K) at amino acid position 95 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	0.074
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	.;T;.;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.084
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	.;T;T;.
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.88	L;L;L;L
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.0	N;N;N;N
REVEL	Benign	0.095
Sift	Benign	0.32	T;T;T;T
Sift4G	Benign	0.41	T;T;T;T
Polyphen		0.28	.;B;.;B
Vest4		0.23
MutPred		0.54		Loss of ubiquitination at K95 (P = 0.0341);Loss of ubiquitination at K95 (P = 0.0341);Loss of ubiquitination at K95 (P = 0.0341);Loss of ubiquitination at K95 (P = 0.0341);
MVP		0.56
MPC		0.21
ClinPred		0.60	D
GERP RS		3.4
Varity_R		0.14
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr20-43541391;