dbSNP rs1037688328: PEX3:c.-231G>A (chr6-143450812-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003630.3(PEX3):c.-231G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PEX3
NM_003630.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.729

Variant links:

Genes affected

PEX3 (HGNC:8858): (peroxisomal biogenesis factor 3) The product of this gene is involved in peroxisome biosynthesis and integrity. It assembles membrane vesicles before the matrix proteins are translocated. Peroxins (PEXs) are proteins that are essential for the assembly of functional peroxisomes. The peroxisome biogenesis disorders (PBDs) are a group of genetically heterogeneous autosomal recessive, lethal diseases characterized by multiple defects in peroxisome function. The peroxisomal biogenesis disorders are a heterogeneous group with at least 14 complementation groups and with more than 1 phenotype being observed in cases falling into particular complementation groups. Although the clinical features of PBD patients vary, cells from all PBD patients exhibit a defect in the import of one or more classes of peroxisomal matrix proteins into the organelle. Defects in this gene are a cause Zellweger syndrome (ZWS). [provided by RefSeq, Oct 2008]

PEX3 links:

ADAT2 (HGNC:21172): (adenosine deaminase tRNA specific 2) Predicted to enable tRNA-specific adenosine-34 deaminase activity. Predicted to be involved in tRNA wobble adenosine to inosine editing. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ADAT2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX3	NM_003630.3 link	c.-231G>A		5_prime_UTR_variant	Exon 1 of 12	ENST00000367591.5	NP_003621.1	P56589
ADAT2	NM_182503.3 link	c.-154C>T		upstream_gene_variant		ENST00000237283.9	NP_872309.2	Q7Z6V5-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PEX3	ENST00000367591.5 link	c.-231G>A	5_prime_UTR_variant	Exon 1 of 12	1	NM_003630.3	ENSP00000356563.4	P56589
PEX3	ENST00000367592.5 link	c.-231G>A	5_prime_UTR_variant	Exon 1 of 7	5		ENSP00000356564.1	Q7Z6V3
ADAT2	ENST00000237283.9 link	c.-154C>T	upstream_gene_variant		1	NM_182503.3	ENSP00000237283.8	Q7Z6V5-1
ADAT2	ENST00000367593.1 link	n.-139C>T	upstream_gene_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

680912

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

355938

African (AFR)

AF:

0.00

AC:

AN:

17588

American (AMR)

AF:

0.00

AC:

AN:

28576

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17048

East Asian (EAS)

AF:

0.00

AC:

AN:

33658

South Asian (SAS)

AF:

0.00

AC:

AN:

59254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33906

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2648

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

454108

Other (OTH)

AF:

0.00

AC:

AN:

34126

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.9

(source)

DANN

Benign

0.97

PhyloP100

-0.73

PromoterAI

-0.069

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over