chr6-42972935-A-G

Position:

• chr6-42972935-A-G

Variant summary

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

The ENST00000304611.13(PEX6):​c.1130+1068T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 152,096 control chromosomes in the GnomAD database, including 35,517 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 0.66 (35517 hom., cov: 31)
• Consequence: PEX6 ENST00000304611.13 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX6	NM_000287.4	c.1130+1068T>C		intron_variant		ENST00000304611.13	NP_000278.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX6	ENST00000304611.13	c.1130+1068T>C		intron_variant		1	NM_000287.4	ENSP00000303511	P1
PEX6	ENST00000244546.4	c.1130+1068T>C		intron_variant		1		ENSP00000244546

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100751 AN: 151978 Hom.: 35461 Cov.: 31

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.649

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

GnomAD4 genome AF: 0.663 AC: 100870 AN: 152096 Hom.: 35517 Cov.: 31 AF XY: 0.656 AC XY: 48784 AN XY: 74336

Gnomad4 AFR AF: 0.917

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.511

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.651

Alfa AF: 0.588 Hom.: 54055

Bravo AF: 0.678

Asia WGS AF: 0.545 AC: 1898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	9.9
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs2395943; hg19: chr6-42940673;