rs35082957

Variant names:

• chr1-2406553-C-G
• NM_002617.4:c.843G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-2406553-C-G
• chr1-2406553-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP3

The NM_002617.4(PEX10):​c.843G>C​(p.Arg281Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R281G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PEX10 NM_002617.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.953

Genes affected

PEX10 (HGNC:8851): (peroxisomal biogenesis factor 10) This gene encodes a protein involved in import of peroxisomal matrix proteins. This protein localizes to the peroxisomal membrane. Mutations in this gene result in phenotypes within the Zellweger spectrum of peroxisomal biogenesis disorders, ranging from neonatal adrenoleukodystrophy to Zellweger syndrome. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM1: In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 6 uncertain in NM_002617.4
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.786

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX10	NM_002617.4	c.843G>C	p.Arg281Ser	missense_variant	Exon 5 of 6	ENST00000447513.7	NP_002608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX10	ENST00000447513.7	c.843G>C	p.Arg281Ser	missense_variant	Exon 5 of 6	1	NM_002617.4	ENSP00000407922.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	.;T;D
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.68	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.79	D;D;D
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.90	.;L;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0080	D;D;D
Sift4G	Uncertain	0.037	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.71
MutPred		0.43		.;Loss of phosphorylation at T284 (P = 0.0795);Loss of phosphorylation at T284 (P = 0.0795);
MVP		0.65
MPC		0.46
ClinPred		0.99	D
GERP RS		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.68
gMVP		0.73

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: chr1-2337992;