rs886046144

Variant names:

• chr1-2405356-C-T
• rs886046144
• NM_002617.4:c.*410G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002617.4(PEX10):​c.*410G>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 0.000257 in 353,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00026 (0 hom.)
• Consequence: PEX10 NM_002617.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.247
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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.*410G>A		3_prime_UTR	Exon 6 of 6	NP_002608.1	O60683-1
	RER1	NM_007033.5	MANE Select	c.*2232C>T		3_prime_UTR	Exon 7 of 7	NP_008964.3
	PEX10	NM_153818.2		c.*410G>A		3_prime_UTR	Exon 6 of 6	NP_722540.1	O60683-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX10	ENST00000447513.7	TSL:1 MANE Select	c.*410G>A		3_prime_UTR	Exon 6 of 6	ENSP00000407922.2	O60683-1
	RER1	ENST00000605895.6	TSL:1 MANE Select	c.*2232C>T		3_prime_UTR	Exon 7 of 7	ENSP00000475168.1	O15258
	PEX10	ENST00000288774.8	TSL:1	c.*410G>A		3_prime_UTR	Exon 6 of 6	ENSP00000288774.3	O60683-2

Frequencies

GnomAD3 genomes AF: 0.000250 AC: 38 AN: 152242 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000514

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000263 AC: 53 AN: 201728 Hom.: 0 Cov.: 0 AF XY: 0.000290 AC XY: 32 AN XY: 110406

African (AFR) AF: 0.00 AC: 0 AN: 5422

American (AMR) AF: 0.00 AC: 0 AN: 9826

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4796

East Asian (EAS) AF: 0.00 AC: 0 AN: 8448

South Asian (SAS) AF: 0.00 AC: 0 AN: 40320

European-Finnish (FIN) AF: 0.000898 AC: 8 AN: 8904

Middle Eastern (MID) AF: 0.00144 AC: 1 AN: 696

European-Non Finnish (NFE) AF: 0.000370 AC: 42 AN: 113444

Other (OTH) AF: 0.000203 AC: 2 AN: 9872

GnomAD4 genome AF: 0.000250 AC: 38 AN: 152242 Hom.: 0 Cov.: 34 AF XY: 0.000215 AC XY: 16 AN XY: 74372

African (AFR) AF: 0.00 AC: 0 AN: 41476

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000514 AC: 35 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00154 Hom.: 1

Bravo AF: 0.000128

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Peroxisome biogenesis disorder 6A (Zellweger) (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.8
DANN	Benign	0.75
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism

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: rs886046144; hg19: chr1-2336795;