chr4-134200491-C-A

Variant names:

• chr4-134200491-C-A
• rs1729822702
• NM_001114734.2:c.529G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001114734.2(PABPC4L):​c.529G>T​(p.Asp177Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,392 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: PABPC4L NM_001114734.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.49
• Publications: 0 publications found

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]

ENSG00000251199 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36294174).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114734.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PABPC4L	NM_001114734.2	MANE Select	c.529G>T	p.Asp177Tyr	missense	Exon 2 of 2	NP_001108206.3	P0CB38
	PABPC4L	NM_001363585.1		c.529G>T	p.Asp177Tyr	missense	Exon 2 of 2	NP_001350514.1	P0CB38

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PABPC4L	ENST00000421491.4	TSL:3 MANE Select	c.529G>T	p.Asp177Tyr	missense	Exon 2 of 2	ENSP00000463233.1	P0CB38
	PABPC4L	ENST00000884201.1		c.529G>T	p.Asp177Tyr	missense	Exon 2 of 2	ENSP00000554260.1
	PABPC4L	ENST00000925025.1		c.529G>T	p.Asp177Tyr	missense	Exon 2 of 2	ENSP00000595084.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399392 Hom.: 0 Cov.: 33 AF XY: 0.00000145 AC XY: 1 AN XY: 690204

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078956

Other (OTH) AF: 0.00 AC: 0 AN: 58002

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000370 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Pathogenic	26
DANN	Benign	0.94
DEOGEN2	Benign	0.090	T
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.089	D
MetaRNN	Benign	0.36	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		7.5
PrimateAI	Benign	0.37	T
Sift4G	Pathogenic	0.0010	D
Polyphen		0.99	D
Vest4		0.17
MVP		0.56
GERP RS		3.9
Varity_R		0.12
gMVP		0.42
Mutation Taster		=39/61	disease causing

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

Other links and lift over

dbSNP: rs1729822702; hg19: chr4-135121646; COSMIC: COSV69930273;