rs762679408

Variant names:

• chr7-92528431-C-A
• NM_000466.3:c.5G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-92528431-C-A
• chr7-92528431-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001282678.2(PEX1):​c.-655G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,437,838 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PEX1 NM_001282678.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55

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 Uncertain_significance. Variant got 2 ACMG points.

• 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.5G>T	p.Trp2Leu	missense_variant	Exon 1 of 24	ENST00000248633.9	NP_000457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX1	ENST00000248633.9	c.5G>T	p.Trp2Leu	missense_variant	Exon 1 of 24	1	NM_000466.3	ENSP00000248633.4
PEX1	ENST00000428214.5	c.5G>T	p.Trp2Leu	missense_variant	Exon 1 of 23	1		ENSP00000394413.1
PEX1	ENST00000438045.5	c.5G>T	p.Trp2Leu	missense_variant	Exon 1 of 21	2		ENSP00000410438.1
PEX1	ENST00000484913.5	n.9G>T		non_coding_transcript_exon_variant	Exon 1 of 24	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1437838 Hom.: 0 Cov.: 31 AF XY: 0.00000280 AC XY: 2 AN XY: 713146

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: 0.0000120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.07e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	23
DANN	Benign	0.94
DEOGEN2	Benign	0.23	.;T;T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.78	T;T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.45	T;T;T
MetaSVM	Uncertain	0.29	D
MutationAssessor	Benign	0.77	N;N;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.4	N;D;D
REVEL	Uncertain	0.44
Sift	Pathogenic	0.0	D;T;T
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.13	.;B;.
Vest4		0.43
MutPred		0.32		Gain of methylation at R6 (P = 0.0454);Gain of methylation at R6 (P = 0.0454);Gain of methylation at R6 (P = 0.0454);
MVP		0.87
MPC		0.29
ClinPred		0.56	D
GERP RS		4.5
Varity_R		0.34
gMVP		0.27

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: chr7-92157745;