rs140890506

chr1-2405770-C-Gchr1-2405770-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002617.4(PEX10):c.977G>C(p.Arg326Pro) 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 benign 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. R326H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: PEX10 NM_002617.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.40

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2788515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEX10	NM_002617.4	c.977G>C	p.Arg326Pro	missense_variant	6/6	ENST00000447513.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX10	ENST00000447513.7	c.977G>C	p.Arg326Pro	missense_variant	6/6	1	NM_002617.4	P4
PEX10	ENST00000288774.8	c.1037G>C	p.Arg346Pro	missense_variant	6/6	1
PEX10	ENST00000507596.5	c.971G>C	p.Arg324Pro	missense_variant	6/6	5		A1
PEX10	ENST00000650293.1	c.932G>C	p.Arg311Pro	missense_variant, NMD_transcript_variant	6/8

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
Cadd	Uncertain	24
Dann	Uncertain	0.99
Eigen	Benign	-0.016
Eigen_PC	Benign	-0.0063
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Uncertain	-0.21	T
MutationTaster	Benign	0.97	D;D;D
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Uncertain	0.45
Sift	Uncertain	0.013	D;D;D
Sift4G	Uncertain	0.013	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.42
MutPred		0.42		.;Loss of MoRF binding (P = 0.004);.;
MVP		0.77
MPC		0.59
ClinPred		0.81	D
GERP RS		3.9
Varity_R		0.51
gMVP		0.72

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: rs140890506; hg19: chr1-2337209;