rs1129333

Variant names:

• chr1-2404237-A-G
• rs1129333
• NM_002617.4:c.*1529T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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]

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

Our verdict: Benign. The variant received -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.

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.*1529T>C		3_prime_UTR	Exon 6 of 6	NP_002608.1
	RER1	NM_007033.5	MANE Select	c.*1113A>G		3_prime_UTR	Exon 7 of 7	NP_008964.3
	PEX10	NM_153818.2		c.*1529T>C		3_prime_UTR	Exon 6 of 6	NP_722540.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX10	ENST00000447513.7	TSL:1 MANE Select	c.*1529T>C		3_prime_UTR	Exon 6 of 6	ENSP00000407922.2
	RER1	ENST00000605895.6	TSL:1 MANE Select	c.*1113A>G		3_prime_UTR	Exon 7 of 7	ENSP00000475168.1
	PEX10	ENST00000288774.8	TSL:1	c.*1529T>C		3_prime_UTR	Exon 6 of 6	ENSP00000288774.3

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 10 AN: 10

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 3 AN: 4

Other (OTH) AF: 1.00 AC: 2 AN: 2

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00233887), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.640 AC: 26559 AN: 41468

American (AMR) AF: 0.828 AC: 12661 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 3182 AN: 3472

East Asian (EAS) AF: 0.831 AC: 4301 AN: 5176

South Asian (SAS) AF: 0.829 AC: 3997 AN: 4824

European-Finnish (FIN) AF: 0.928 AC: 9848 AN: 10612

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.910 AC: 61874 AN: 68018

Other (OTH) AF: 0.835 AC: 1759 AN: 2106

Alfa AF: 0.876 Hom.: 64509

Bravo AF: 0.806

Asia WGS AF: 0.785 AC: 2732 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.40
PhyloP100		0.027
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: rs1129333; hg19: chr1-2335676; COSMIC: COSV56580561; COSMIC: COSV56580561;