NM_002617.4:c.2T>G

Variant names:

• chr1-2412501-A-C
• NM_002617.4:c.2T>G

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PS1_Moderate PM2

The NM_002617.4(PEX10):​c.2T>G​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000826 in 1,210,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: PEX10 NM_002617.4 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.10

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 Pathogenic. Variant got 12 ACMG points.

• PVS1: Start lost variant, next in-frame start position is after 29 pathogenic variants. Next in-frame start position is after 145 codons. Genomic position: 2408619. Lost 0.441 part of the original CDS.
• PS1: Another start lost variant in NM_002617.4 (PEX10) was described as [Likely_pathogenic] in ClinVar as 3336181
• 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.2T>G	p.Met1?	start_lost	Exon 1 of 6	ENST00000447513.7	NP_002608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX10	ENST00000447513.7	c.2T>G	p.Met1?	start_lost	Exon 1 of 6	1	NM_002617.4	ENSP00000407922.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 8.26e-7 AC: 1 AN: 1210334 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 590976

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: 0.00000101

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
BayesDel_addAF	Pathogenic	0.59	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	23
DANN	Benign	0.94
DEOGEN2	Benign	0.14	.;T;T
Eigen	Benign	-0.022
Eigen_PC	Benign	-0.088
FATHMM_MKL	Benign	0.39	N
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Pathogenic	1.0	D
MetaRNN	Pathogenic	0.87	D;D;D
MetaSVM	Uncertain	0.062	D
PROVEAN	Benign	-1.4	N;N;N
REVEL	Uncertain	0.43
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.99	D;P;.
Vest4		0.55
MutPred		0.59		Gain of methylation at M1 (P = 0.0053);Gain of methylation at M1 (P = 0.0053);Gain of methylation at M1 (P = 0.0053);
MVP		0.82
ClinPred		1.0	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.98
gMVP		0.69

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: chr1-2343940;