7-92518266-C-T

Variant names:

• chr7-92518266-C-T
• NM_000466.3:c.358-11G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000466.3(PEX1):​c.358-11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000754 in 1,325,444 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: PEX1 NM_000466.3 intron
• Scores: Splicing: ADA: 0.0005790
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378

Genes affected

PEX1 (HGNC:8850): (peroxisomal biogenesis factor 1) This gene encodes a member of the AAA ATPase family, a large group of ATPases associated with diverse cellular activities. This protein is cytoplasmic but is often anchored to a peroxisomal membrane where it forms a heteromeric complex and plays a role in the import of proteins into peroxisomes and peroxisome biogenesis. Mutations in this gene have been associated with complementation group 1 peroxisomal disorders such as neonatal adrenoleukodystrophy, infantile Refsum disease, and Zellweger syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX1	NM_000466.3	c.358-11G>A		intron_variant	Intron 3 of 23	ENST00000248633.9	NP_000457.1
PEX1	NM_001282677.2	c.358-11G>A		intron_variant	Intron 3 of 22		NP_001269606.1
PEX1	NM_001282678.2	c.-267-11G>A		intron_variant	Intron 3 of 23		NP_001269607.1
PEX1	XM_047420472.1	c.358-11G>A		intron_variant	Intron 3 of 22		XP_047276428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX1	ENST00000248633.9	c.358-11G>A		intron_variant	Intron 3 of 23	1	NM_000466.3	ENSP00000248633.4
PEX1	ENST00000428214.5	c.358-11G>A		intron_variant	Intron 3 of 22	1		ENSP00000394413.1
PEX1	ENST00000438045.5	c.273+3836G>A		intron_variant	Intron 2 of 20	2		ENSP00000410438.1
PEX1	ENST00000484913.5	n.397-11G>A		intron_variant	Intron 3 of 23	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.54e-7 AC: 1 AN: 1325444 Hom.: 0 Cov.: 21 AF XY: 0.00000150 AC XY: 1 AN XY: 667074

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000101

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.6
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00058
dbscSNV1_RF	Benign	0.12
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-92147580;