4-134200092-G-C

Variant summary

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

The NM_001114734.2(PABPC4L):c.928C>G(p.Arg310Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PABPC4L NM_001114734.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.457

Genes affected

PABPC4L (HGNC:31955): (poly(A) binding protein cytoplasmic 4 like) Predicted to enable mRNA 3'-UTR binding activity; poly(A) binding activity; and poly(U) RNA binding activity. Predicted to be part of ribonucleoprotein complex. Predicted to be active in cytoplasmic stress granule; cytosol; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

(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	UniProt
PABPC4L	NM_001114734.2	c.928C>G	p.Arg310Gly	missense_variant	2/2	ENST00000421491.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PABPC4L	ENST00000421491.4	c.928C>G	p.Arg310Gly	missense_variant	2/2	3	NM_001114734.2	P1
	ENST00000658435.1	n.412-96575C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 45

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

Mar 27, 2023

The c.1102C>G (p.R368G) alteration is located in exon 2 (coding exon 1) of the PABPC4L gene. This alteration results from a C to G substitution at nucleotide position 1102, causing the arginine (R) at amino acid position 368 to be replaced by a glycine (G). 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	0.21
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.27
Cadd	Benign	21
Dann	Benign	0.90
DEOGEN2	Benign	0.036	T
FATHMM_MKL	Benign	0.40	N
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.55	D
MutationAssessor	Uncertain	2.6	M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.28	T
Sift4G	Uncertain	0.048	D
Polyphen		0.77	P
Vest4		0.55
MVP		0.56
GERP RS		1.3
Varity_R		0.13
gMVP		0.87

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: chr4-135121247;