rs79435202

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_057174.3(PEX16):c.1034A>C(p.His345Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 1,611,204 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. H345H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.013 ( 40 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 35 hom. )

Consequence

PEX16
NM_057174.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.937

Publications

4 publications found

Variant links:

Genes affected

PEX16 (HGNC:8857): (peroxisomal biogenesis factor 16) The protein encoded by this gene is an integral peroxisomal membrane protein. An inactivating nonsense mutation localized to this gene was observed in a patient with Zellweger syndrome of the complementation group CGD/CG9. Expression of this gene product morphologically and biochemically restores the formation of new peroxisomes, suggesting a role in peroxisome organization and biogenesis. Alternative splicing has been observed for this gene and two variants have been described. [provided by RefSeq, Jul 2008]

PEX16 Gene-Disease associations (from GenCC):

peroxisome biogenesis disorder
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
peroxisome biogenesis disorder 8A (Zellweger)
Inheritance: AR Classification: DEFINITIVE, MODERATE Submitted by: G2P, Ambry Genetics
peroxisome biogenesis disorder 8B
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
Zellweger spectrum disorders
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PEX16 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002622664).

BP6

Variant 11-45910096-T-G is Benign according to our data. Variant chr11-45910096-T-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 304783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0134 (2037/152226) while in subpopulation AFR AF = 0.045 (1870/41536). AF 95% confidence interval is 0.0433. There are 40 homozygotes in GnomAd4. There are 951 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 40 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_057174.3. 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
	PEX16	NM_004813.4	MANE Select	c.*158A>C		3_prime_UTR	Exon 11 of 11	NP_004804.2	Q9Y5Y5-1
	PEX16	NM_057174.3		c.1034A>C	p.His345Pro	missense	Exon 11 of 11	NP_476515.2	Q9Y5Y5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PEX16	ENST00000241041.7	TSL:1	c.1034A>C	p.His345Pro	missense	Exon 11 of 11	ENSP00000241041.3	Q9Y5Y5-2
PEX16	ENST00000378750.10	TSL:1 MANE Select	c.*158A>C		3_prime_UTR	Exon 11 of 11	ENSP00000368024.5	Q9Y5Y5-1
PEX16	ENST00000938297.1		c.*158A>C		3_prime_UTR	Exon 10 of 10	ENSP00000608356.1

Frequencies

GnomAD3 genomes

AF:

0.0133

AC:

2028

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0449

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.00403

AC:

1008

AN:

250066

AF XY:

0.00290

show subpopulations

Gnomad AFR exome

AF:

0.0470

Gnomad AMR exome

AF:

0.00391

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000743

Gnomad OTH exome

AF:

0.00311

GnomAD4 exome

AF:

0.00191

AC:

2785

AN:

1458978

Hom.:

Cov.:

AF XY:

0.00174

AC XY:

1261

AN XY:

725812

show subpopulations

African (AFR)

AF:

0.0472

AC:

1576

AN:

33408

American (AMR)

AF:

0.00432

AC:

193

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.000126

AC:

AN:

39698

South Asian (SAS)

AF:

0.000267

AC:

AN:

86164

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52786

Middle Eastern (MID)

AF:

0.00772

AC:

AN:

4146

European-Non Finnish (NFE)

AF:

0.000618

AC:

687

AN:

1111730

Other (OTH)

AF:

0.00447

AC:

269

AN:

60204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

145

290

435

580

725

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0134

AC:

2037

AN:

152226

Hom.:

Cov.:

AF XY:

0.0128

AC XY:

951

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0450

AC:

1870

AN:

41536

American (AMR)

AF:

0.00602

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000544

AC:

AN:

67994

Other (OTH)

AF:

0.0151

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

103

206

308

411

514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00340

Hom.:

Bravo

AF:

0.0152

ESP6500AA

AF:

0.0350

AC:

154

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00449

AC:

545

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.00136

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Peroxisome biogenesis disorder 8A (Zellweger) (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.1

(source)

DANN

Benign

0.37

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.00071

LIST_S2

Benign

0.14

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.0

PhyloP100

0.94

PrimateAI

Benign

0.35

PROVEAN

Benign

0.080

REVEL

Benign

0.049

Sift

Benign

0.40

Sift4G

Benign

0.16

Polyphen

0.0

Vest4

0.13

MVP

0.11

MPC

0.55

ClinPred

0.00079

GERP RS

2.9

gMVP

0.56

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over