rs61736380

Variant names:

• chr1-2406784-C-A
• NM_002617.4:c.712G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-2406784-C-A
• chr1-2406784-C-G
• chr1-2406784-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_002617.4(PEX10):​c.712G>T​(p.Gly238Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. G238R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PEX10 NM_002617.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.469

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 4 ACMG points.

• PM1: In a topological_domain Cytoplasmic (size 89) in uniprot entity PEX10_HUMAN there are 8 pathogenic changes around while only 2 benign (80%) in NM_002617.4
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX10	NM_002617.4	c.712G>T	p.Gly238Cys	missense_variant	Exon 4 of 6	ENST00000447513.7	NP_002608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX10	ENST00000447513.7	c.712G>T	p.Gly238Cys	missense_variant	Exon 4 of 6	1	NM_002617.4	ENSP00000407922.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1458318 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 725264

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	.;T;T
Eigen	Benign	0.11
Eigen_PC	Benign	-0.024
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Pathogenic	0.31	D
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Uncertain	2.2	.;M;.
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.5	D;D;D
REVEL	Uncertain	0.49
Sift	Benign	0.033	D;T;T
Sift4G	Uncertain	0.013	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.33
MutPred		0.60		.;Loss of disorder (P = 0.0681);Loss of disorder (P = 0.0681);
MVP		0.89
MPC		0.45
ClinPred		0.95	D
GERP RS		-0.23
Varity_R		0.17
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr1-2338223;