7-92501648-G-T

Variant names:

• chr7-92501648-G-T
• rs145430946
• NM_000466.3:c.2442C>A

Variant summary

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

The NM_000466.3(PEX1):​c.2442C>A​(p.Phe814Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,536 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F814F) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PEX1 NM_000466.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62

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.2442C>A	p.Phe814Leu	missense_variant	Exon 15 of 24	ENST00000248633.9	NP_000457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX1	ENST00000248633.9	c.2442C>A	p.Phe814Leu	missense_variant	Exon 15 of 24	1	NM_000466.3	ENSP00000248633.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461536 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727096

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	.;T;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Uncertain	0.067	D
MutationAssessor	Pathogenic	3.2	.;M;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-4.6	D;D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0030	D;D;D
Sift4G	Benign	0.078	T;D;D
Polyphen		0.85	.;P;.
Vest4		0.48
MutPred		0.65		.;Loss of catalytic residue at F814 (P = 0.1106);.;
MVP		0.86
MPC		0.19
ClinPred		0.99	D
GERP RS		2.6
Varity_R		0.43
gMVP		0.89

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

LitVar

Other links and lift over

dbSNP: rs145430946; hg19: chr7-92130962; COSMIC: COSV50413153; COSMIC: COSV50413153;