rs1143016

Variant names:

• chr1-2408773-G-A
• rs1143016
• NM_002617.4:c.279C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002617.4(PEX10):​c.279C>T​(p.Gly93Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0599 in 1,613,860 control chromosomes in the GnomAD database, including 3,773 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (367 hom., cov: 32)
  • Exomes 𝑓: 0.061 (3406 hom.)
• Consequence: PEX10 NM_002617.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -2.17
• Publications: 4 publications found

Genes affected

PEX10 (HGNC:8851): (peroxisomal biogenesis factor 10) This gene encodes a protein involved in import of peroxisomal matrix proteins. This protein localizes to the peroxisomal membrane. Mutations in this gene result in phenotypes within the Zellweger spectrum of peroxisomal biogenesis disorders, ranging from neonatal adrenoleukodystrophy to Zellweger syndrome. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

PEX10 Gene-Disease associations (from GenCC):

• peroxisome biogenesis disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• peroxisome biogenesis disorder 6A (Zellweger)

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Myriad Women’s Health, Ambry Genetics, G2P
• peroxisome biogenesis disorder 6B

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal recessive ataxia due to PEX10 deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Zellweger spectrum disorders

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-2408773-G-A is Benign according to our data. Variant chr1-2408773-G-A is described in ClinVar as Benign. ClinVar VariationId is 129883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.17 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0661 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002617.4. 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
	PEX10	NM_002617.4	MANE Select	c.279C>T	p.Gly93Gly	synonymous	Exon 3 of 6	NP_002608.1	O60683-1
	PEX10	NM_153818.2		c.279C>T	p.Gly93Gly	synonymous	Exon 3 of 6	NP_722540.1	O60683-2
	PEX10	NM_001374425.1		c.279C>T	p.Gly93Gly	synonymous	Exon 3 of 6	NP_001361354.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX10	ENST00000447513.7	TSL:1 MANE Select	c.279C>T	p.Gly93Gly	synonymous	Exon 3 of 6	ENSP00000407922.2	O60683-1
	PEX10	ENST00000288774.8	TSL:1	c.279C>T	p.Gly93Gly	synonymous	Exon 3 of 6	ENSP00000288774.3	O60683-2
	PEX10	ENST00000874692.1		c.279C>T	p.Gly93Gly	synonymous	Exon 3 of 6	ENSP00000544751.1

Frequencies

GnomAD3 genomes AF: 0.0502 AC: 7639 AN: 152138 Hom.: 367 Cov.: 32

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0217

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0368

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0677

Gnomad OTH AF: 0.0330

GnomAD2 exomes AF: 0.0536 AC: 13438 AN: 250712 AF XY: 0.0542

Gnomad AFR exome AF: 0.0115

Gnomad AMR exome AF: 0.0215

Gnomad ASJ exome AF: 0.0283

Gnomad EAS exome AF: 0.00125

Gnomad FIN exome AF: 0.165

Gnomad NFE exome AF: 0.0651

Gnomad OTH exome AF: 0.0490

GnomAD4 exome AF: 0.0609 AC: 89014 AN: 1461604 Hom.: 3406 Cov.: 36 AF XY: 0.0605 AC XY: 44007 AN XY: 727134

African (AFR) AF: 0.00851 AC: 285 AN: 33474

American (AMR) AF: 0.0208 AC: 932 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0289 AC: 755 AN: 26126

East Asian (EAS) AF: 0.00123 AC: 49 AN: 39694

South Asian (SAS) AF: 0.0354 AC: 3050 AN: 86254

European-Finnish (FIN) AF: 0.157 AC: 8389 AN: 53330

Middle Eastern (MID) AF: 0.0210 AC: 121 AN: 5768

European-Non Finnish (NFE) AF: 0.0651 AC: 72337 AN: 1111856

Other (OTH) AF: 0.0513 AC: 3096 AN: 60388

GnomAD4 genome AF: 0.0502 AC: 7641 AN: 152256 Hom.: 367 Cov.: 32 AF XY: 0.0546 AC XY: 4063 AN XY: 74434

African (AFR) AF: 0.0102 AC: 425 AN: 41556

American (AMR) AF: 0.0218 AC: 333 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0262 AC: 91 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5186

South Asian (SAS) AF: 0.0371 AC: 179 AN: 4830

European-Finnish (FIN) AF: 0.176 AC: 1864 AN: 10614

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0677 AC: 4603 AN: 67986

Other (OTH) AF: 0.0327 AC: 69 AN: 2112

Alfa AF: 0.0560 Hom.: 142

Bravo AF: 0.0374

Asia WGS AF: 0.0180 AC: 61 AN: 3478

EpiCase AF: 0.0607

EpiControl AF: 0.0573

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)
-	-	2	Peroxisome biogenesis disorder 6A (Zellweger) (2)
-	-	1	Peroxisome biogenesis disorder 6B (1)
-	-	1	Peroxisome biogenesis disorder, complementation group 7 (1)
-	-	1	Zellweger spectrum disorders (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.29
DANN	Benign	0.44
PhyloP100		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs1143016; hg19: chr1-2340212;