ENST00000970120.1:c.*2205G>C

Variant names:

• chr6-42960279-C-G
• rs11752813
• ENST00000970120.1:c.*2205G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000970120.1(PEX6):​c.*2205G>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 0.403 in 152,226 control chromosomes in the GnomAD database, including 12,748 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 0.40 (12748 hom., cov: 34)
• Consequence: PEX6 ENST00000970120.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210
• Publications: 23 publications found

Genes affected

PEX6 (HGNC:8859): (peroxisomal biogenesis factor 6) This gene encodes a member of the AAA (ATPases associated with diverse cellular activities) family of ATPases. This member is a predominantly cytoplasmic protein, which plays a direct role in peroxisomal protein import and is required for PTS1 (peroxisomal targeting signal 1, a C-terminal tripeptide of the sequence ser-lys-leu) receptor activity. Mutations in this gene cause peroxisome biogenesis disorders of complementation group 4 and complementation group 6. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

PEX6 Gene-Disease associations (from GenCC):

• peroxisome biogenesis disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• peroxisome biogenesis disorder 4A (Zellweger)

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Myriad Women's Health, G2P, Labcorp Genetics (formerly Invitae)
• peroxisome biogenesis disorder 4B

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• Heimler syndrome 2

  Inheritance: AR Classification: MODERATE Submitted by: G2P
• autosomal recessive cerebellar ataxia-blindness-deafness syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Zellweger spectrum disorders

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CNPY3-GNMT (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000970120.1. 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
	CNPY3-GNMT	NM_001318857.2		c.152-2483C>G		intron	N/A	NP_001305786.1
	CNPY3-GNMT	NM_001318856.2		c.9-1933C>G		intron	N/A	NP_001305785.1
	CNPY3-GNMT	NM_001318858.2		c.152-2483C>G		intron	N/A	NP_001305787.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX6	ENST00000970120.1		c.*2205G>C		3_prime_UTR	Exon 18 of 18	ENSP00000640179.1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61291 AN: 152108 Hom.: 12744 Cov.: 34

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.417

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.403 AC: 61328 AN: 152226 Hom.: 12748 Cov.: 34 AF XY: 0.399 AC XY: 29685 AN XY: 74444

African (AFR) AF: 0.374 AC: 15551 AN: 41534

American (AMR) AF: 0.339 AC: 5191 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1415 AN: 3472

East Asian (EAS) AF: 0.104 AC: 540 AN: 5186

South Asian (SAS) AF: 0.404 AC: 1949 AN: 4822

European-Finnish (FIN) AF: 0.406 AC: 4304 AN: 10606

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30847 AN: 67990

Other (OTH) AF: 0.414 AC: 876 AN: 2114

Alfa AF: 0.431 Hom.: 1921

Bravo AF: 0.394

Asia WGS AF: 0.257 AC: 896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.2
DANN	Benign	0.36
PhyloP100		-0.021
PromoterAI		-0.0042	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11752813;

hg19: chr6-42928017;