chr4-134199984-T-G

Variant names:

• chr4-134199984-T-G
• rs1333293489
• NM_001114734.2:c.1036A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001114734.2(PABPC4L):​c.1036A>C​(p.Thr346Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T346S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: PABPC4L NM_001114734.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21127173).

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.1036A>C	p.Thr346Pro	missense	Exon 2 of 2	NP_001108206.3	P0CB38
	PABPC4L	NM_001363585.1		c.1036A>C	p.Thr346Pro	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.1036A>C	p.Thr346Pro	missense	Exon 2 of 2	ENSP00000463233.1	P0CB38
	PABPC4L	ENST00000884201.1		c.1036A>C	p.Thr346Pro	missense	Exon 2 of 2	ENSP00000554260.1
	PABPC4L	ENST00000925025.1		c.1036A>C	p.Thr346Pro	missense	Exon 2 of 2	ENSP00000595084.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399384 Hom.: 0 Cov.: 42 AF XY: 0.00 AC XY: 0 AN XY: 690200

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: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078954

Other (OTH) AF: 0.00 AC: 0 AN: 58000

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Benign	0.38
DEOGEN2	Benign	0.063	T
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.21	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.3
PrimateAI	Benign	0.32	T
Sift4G	Uncertain	0.0080	D
Polyphen		0.66	P
Vest4		0.40
MVP		0.47
GERP RS		-4.6
Varity_R		0.13
gMVP		0.89
Mutation Taster		=92/8	polymorphism

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: rs1333293489; hg19: chr4-135121139;