1-2405755-C-T

Position:

• chr1-2405755-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002617.4(PEX10):​c.*11G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 1,594,616 control chromosomes in the GnomAD database, including 908 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (144 hom., cov: 34)
  • Exomes 𝑓: 0.027 (764 hom.)
• Consequence: PEX10 NM_002617.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.68

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-2405755-C-T is Benign according to our data. Variant chr1-2405755-C-T is described in ClinVar as [Benign]. Clinvar id is 262787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX10	NM_002617.4	c.*11G>A		3_prime_UTR_variant	6/6	ENST00000447513.7	NP_002608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX10	ENST00000447513	c.*11G>A		3_prime_UTR_variant	6/6	1	NM_002617.4	ENSP00000407922.2

Frequencies

GnomAD3 genomes AF: 0.0354 AC: 5383 AN: 152238 Hom.: 143 Cov.: 34

Gnomad AFR AF: 0.0671

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0244

Gnomad ASJ AF: 0.0132

Gnomad EAS AF: 0.0327

Gnomad SAS AF: 0.0786

Gnomad FIN AF: 0.00527

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0220

Gnomad OTH AF: 0.0296

GnomAD3 exomes AF: 0.0281 AC: 6070 AN: 216298 Hom.: 121 AF XY: 0.0302 AC XY: 3540 AN XY: 117108

Gnomad AFR exome AF: 0.0604

Gnomad AMR exome AF: 0.0108

Gnomad ASJ exome AF: 0.0157

Gnomad EAS exome AF: 0.0249

Gnomad SAS exome AF: 0.0722

Gnomad FIN exome AF: 0.00468

Gnomad NFE exome AF: 0.0235

Gnomad OTH exome AF: 0.0232

GnomAD4 exome AF: 0.0272 AC: 39269 AN: 1442260 Hom.: 764 Cov.: 31 AF XY: 0.0284 AC XY: 20320 AN XY: 715756

Gnomad4 AFR exome AF: 0.0681

Gnomad4 AMR exome AF: 0.0120

Gnomad4 ASJ exome AF: 0.0158

Gnomad4 EAS exome AF: 0.0294

Gnomad4 SAS exome AF: 0.0729

Gnomad4 FIN exome AF: 0.00652

Gnomad4 NFE exome AF: 0.0243

Gnomad4 OTH exome AF: 0.0277

GnomAD4 genome AF: 0.0354 AC: 5395 AN: 152356 Hom.: 144 Cov.: 34 AF XY: 0.0350 AC XY: 2607 AN XY: 74522

Gnomad4 AFR AF: 0.0674

Gnomad4 AMR AF: 0.0244

Gnomad4 ASJ AF: 0.0132

Gnomad4 EAS AF: 0.0330

Gnomad4 SAS AF: 0.0774

Gnomad4 FIN AF: 0.00527

Gnomad4 NFE AF: 0.0220

Gnomad4 OTH AF: 0.0288

Alfa AF: 0.0237 Hom.: 11

Bravo AF: 0.0357

Asia WGS AF: 0.0500 AC: 174 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 18, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Sep 27, 2017	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	May 06, 2022	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Peroxisome biogenesis disorder 6A (Zellweger) Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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	-0.90
CADD	Benign	0.70
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs3795270; hg19: chr1-2337194;