4-134200045-C-A

Variant summary

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

The NM_001114734.2(PABPC4L):c.975G>T(p.Met325Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PABPC4L NM_001114734.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.88

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.975G>T	p.Met325Ile	missense_variant	2/2	ENST00000421491.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PABPC4L	ENST00000421491.4	c.975G>T	p.Met325Ile	missense_variant	2/2	3	NM_001114734.2	P1
	ENST00000658435.1	n.412-96528G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1399392 Hom.: 0 Cov.: 42 AF XY: 0.00 AC XY: 0 AN XY: 690202

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Jan 03, 2024

The c.1149G>T (p.M383I) alteration is located in exon 2 (coding exon 1) of the PABPC4L gene. This alteration results from a G to T substitution at nucleotide position 1149, causing the methionine (M) at amino acid position 383 to be replaced by an isoleucine (I). 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	Uncertain	0.51
BayesDel_addAF	Benign	-0.0078	T
BayesDel_noAF	Benign	-0.25
Cadd	Uncertain	25
Dann	Benign	0.86
DEOGEN2	Benign	0.028	T
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.67	D
MutationAssessor	Benign	0.88	L
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.59	T
Sift4G	Uncertain	0.051	T
Polyphen		1.0	D
Vest4		0.59
MVP		0.55
GERP RS		3.3
Varity_R		0.25
gMVP		0.66

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: chr4-135121200;