6-143450846-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003630.3(PEX3):c.-197T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 756,068 control chromosomes in the GnomAD database, including 611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 102 hom., cov: 32)

Exomes 𝑓: 0.013 ( 509 hom. )

Consequence

PEX3
NM_003630.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.708

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 6-143450846-T-C is Benign according to our data. Variant chr6-143450846-T-C is described in ClinVar as [Benign]. Clinvar id is 355569.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX3	NM_003630.3 link	c.-197T>C		5_prime_UTR_variant	Exon 1 of 12	ENST00000367591.5	NP_003621.1	P56589
ADAT2	NM_182503.3 link	c.-188A>G		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.-197T>C	5_prime_UTR_variant	Exon 1 of 12	1	NM_003630.3	ENSP00000356563.4	P56589
PEX3	ENST00000367592.5 link	c.-197T>C	5_prime_UTR_variant	Exon 1 of 7	5		ENSP00000356564.1	Q7Z6V3
ADAT2	ENST00000237283.9 link	c.-188A>G	upstream_gene_variant		1	NM_182503.3	ENSP00000237283.8	Q7Z6V5-1
ADAT2	ENST00000367593.1 link	n.-173A>G	upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1908

AN:

152206

Hom.:

100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00256

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0959

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00675

Gnomad SAS

AF:

0.0428

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.0172

GnomAD4 exome

AF:

0.0135

AC:

8135

AN:

603744

Hom.:

509

Cov.:

AF XY:

0.0134

AC XY:

4332

AN XY:

322430

show subpopulations

African (AFR)

AF:

0.00200

AC:

AN:

16492

American (AMR)

AF:

0.152

AC:

4879

AN:

32188

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17054

East Asian (EAS)

AF:

0.00373

AC:

128

AN:

34320

South Asian (SAS)

AF:

0.0404

AC:

2416

AN:

59822

European-Finnish (FIN)

AF:

0.000137

AC:

AN:

36558

Middle Eastern (MID)

AF:

0.00371

AC:

AN:

2426

European-Non Finnish (NFE)

AF:

0.000841

AC:

314

AN:

373164

Other (OTH)

AF:

0.0111

AC:

351

AN:

31720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

367

734

1100

1467

1834

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0126

AC:

1920

AN:

152324

Hom.:

102

Cov.:

AF XY:

0.0143

AC XY:

1069

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00255

AC:

106

AN:

41566

American (AMR)

AF:

0.0966

AC:

1478

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00676

AC:

AN:

5176

South Asian (SAS)

AF:

0.0426

AC:

206

AN:

4832

European-Finnish (FIN)

AF:

0.000847

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000691

AC:

AN:

68030

Other (OTH)

AF:

0.0175

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

189

283

378

472

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000375

Hom.:

Bravo

AF:

0.0204

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Peroxisome biogenesis disorder 10A (Zellweger)

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

(source)

DANN

Benign

0.65

PhyloP100

0.71

PromoterAI

-0.20

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

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

Publications

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6-143450846-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over