rs1554375511

Variant names:

• chr7-92517754-GA-G
• NM_000466.3:c.760delT

Your query was ambiguous. Multiple possible variants found:

• chr7-92517754-GA-G
• chr7-92517754-GA-GAA

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_000466.3(PEX1):​c.760delT​(p.Ser254ProfsTer14) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000692 in 1,444,274 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PEX1 NM_000466.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.38

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 Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX1	NM_000466.3	c.760delT	p.Ser254ProfsTer14	frameshift_variant	Exon 5 of 24	ENST00000248633.9	NP_000457.1
PEX1	NM_001282677.2	c.760delT	p.Ser254ProfsTer14	frameshift_variant	Exon 5 of 23		NP_001269606.1
PEX1	NM_001282678.2	c.136delT	p.Ser46ProfsTer14	frameshift_variant	Exon 5 of 24		NP_001269607.1
PEX1	XM_047420472.1	c.760delT	p.Ser254ProfsTer14	frameshift_variant	Exon 5 of 23		XP_047276428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX1	ENST00000248633.9	c.760delT	p.Ser254ProfsTer14	frameshift_variant	Exon 5 of 24	1	NM_000466.3	ENSP00000248633.4
PEX1	ENST00000428214.5	c.760delT	p.Ser254ProfsTer14	frameshift_variant	Exon 5 of 23	1		ENSP00000394413.1
PEX1	ENST00000438045.5	c.274-3788delT		intron_variant	Intron 2 of 20	2		ENSP00000410438.1
PEX1	ENST00000484913.5	n.799delT		non_coding_transcript_exon_variant	Exon 5 of 24	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444274 Hom.: 0 Cov.: 33 AF XY: 0.00000139 AC XY: 1 AN XY: 717472

Gnomad4 AFR exome AF: 0.0000310

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-92147068;