rs1129332

chr1-2404771-C-T

Variant summary

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

The NM_002617.4(PEX10):c.*995G>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 0.246 in 152,352 control chromosomes in the GnomAD database, including 5,211 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 0.25 (5206 hom., cov: 34)
  • Exomes 𝑓: 0.28 (5 hom.)
• Consequence: PEX10 NM_002617.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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 (EAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEX10	NM_002617.4	c.*995G>A		3_prime_UTR_variant	6/6	ENST00000447513.7
RER1	NM_007033.5	c.*1647C>T		3_prime_UTR_variant	7/7	ENST00000605895.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX10	ENST00000447513.7	c.*995G>A		3_prime_UTR_variant	6/6	1	NM_002617.4	P4
RER1	ENST00000605895.6	c.*1647C>T		3_prime_UTR_variant	7/7	1	NM_007033.5	P1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37433 AN: 152134 Hom.: 5205 Cov.: 34

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.280 AC: 28 AN: 100 Hom.: 5 Cov.: 0 AF XY: 0.241 AC XY: 14 AN XY: 58

Gnomad4 FIN exome AF: 0.292

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.246 AC: 37437 AN: 152252 Hom.: 5206 Cov.: 34 AF XY: 0.244 AC XY: 18182 AN XY: 74426

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.271

Alfa AF: 0.298 Hom.: 6666

Bravo AF: 0.247

Asia WGS AF: 0.274 AC: 953 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	0.55
Dann	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1129332; hg19: chr1-2336210;