chr20-44919275-A-G

Position:

• chr20-44919275-A-G

Variant summary

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

The NM_001372179.1(PABPC1L):​c.736A>G​(p.Lys246Glu) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PABPC1L NM_001372179.1 missense, splice_region
• Scores: Splicing: ADA: 0.004960
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.02

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PABPC1L	NM_001372179.1	c.736A>G	p.Lys246Glu	missense_variant, splice_region_variant	5/15	ENST00000217073.7	NP_001359108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PABPC1L	ENST00000217073.7	c.736A>G	p.Lys246Glu	missense_variant, splice_region_variant	5/15	5	NM_001372179.1	ENSP00000217073.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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

Feb 12, 2024

The c.736A>G (p.K246E) alteration is located in exon 5 (coding exon 5) of the PABPC1L gene. This alteration results from a A to G substitution at nucleotide position 736, causing the lysine (K) at amino acid position 246 to be replaced by a glutamic acid (E). 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	0.11
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.042	.;T;.;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.84	.;T;T;.
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.45	T;T;T;T
MetaSVM	Uncertain	0.17	D
MutationAssessor	Benign	0.56	N;N;N;N
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Pathogenic	0.66
Sift	Benign	0.035	D;D;D;D
Sift4G	Benign	0.19	T;T;T;T
Polyphen		0.73	.;P;.;P
Vest4		0.51
MutPred		0.52		Loss of ubiquitination at K246 (P = 0.0233);Loss of ubiquitination at K246 (P = 0.0233);Loss of ubiquitination at K246 (P = 0.0233);Loss of ubiquitination at K246 (P = 0.0233);
MVP		0.86
MPC		0.90
ClinPred		0.77	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.30
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0050
dbscSNV1_RF	Benign	0.076
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: chr20-43547916;