rs1129333

Positions:

• chr1-2404237-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002617.4(PEX10):​c.*1529T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 152,190 control chromosomes in the GnomAD database, including 52,526 homozygotes. 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: 𝑓 0.82 (52519 hom., cov: 32)
  • Exomes 𝑓: 0.89 (7 hom.)
• Consequence: PEX10 NM_002617.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270

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]

RER1 (HGNC:30309): (retention in endoplasmic reticulum sorting receptor 1) The protein encoded by this gene is a multi-pass membrane protein that is localized to the golgi apparatus. It is involved in the retention of endoplasmic reticulum (ER) membrane proteins in the ER and retrieval of ER membrane proteins from the early Golgi compartment to facilitate gamma-secretase complex assembly. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX10	NM_002617.4	c.*1529T>C		3_prime_UTR_variant	6/6	ENST00000447513.7	NP_002608.1
RER1	NM_007033.5	c.*1113A>G		3_prime_UTR_variant	7/7	ENST00000605895.6	NP_008964.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX10	ENST00000447513	c.*1529T>C		3_prime_UTR_variant	6/6	1	NM_002617.4	ENSP00000407922.2
RER1	ENST00000605895.6	c.*1113A>G		3_prime_UTR_variant	7/7	1	NM_007033.5	ENSP00000475168.1

Frequencies

GnomAD3 genomes AF: 0.823 AC: 125091 AN: 152054 Hom.: 52511 Cov.: 32

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.928

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.910

Gnomad OTH AF: 0.841

GnomAD4 exome AF: 0.889 AC: 16 AN: 18 Hom.: 7 Cov.: 0 AF XY: 0.917 AC XY: 11 AN XY: 12

Gnomad4 AMR exome AF: 0.500

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.750

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.822 AC: 125140 AN: 152172 Hom.: 52519 Cov.: 32 AF XY: 0.823 AC XY: 61249 AN XY: 74412

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.828

Gnomad4 ASJ AF: 0.916

Gnomad4 EAS AF: 0.831

Gnomad4 SAS AF: 0.829

Gnomad4 FIN AF: 0.928

Gnomad4 NFE AF: 0.910

Gnomad4 OTH AF: 0.835

Alfa AF: 0.882 Hom.: 47579

Bravo AF: 0.806

Asia WGS AF: 0.785 AC: 2732 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.40

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: rs1129333; hg19: chr1-2335676; COSMIC: COSV56580561; COSMIC: COSV56580561;