rs554152771

Variant names:

• chr2-61031709-G-A
• NM_002618.4:c.383G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-61031709-G-A
• chr2-61031709-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002618.4(PEX13):​c.383G>A​(p.Gly128Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,890 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PEX13 NM_002618.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.80

Genes affected

PEX13 (HGNC:8855): (peroxisomal biogenesis factor 13) This gene encodes a peroxisomal membrane protein that binds the type 1 peroxisomal targeting signal receptor via a SH3 domain located in the cytoplasm. Mutations and deficiencies in peroxisomal protein importing and peroxisome assembly lead to peroxisomal biogenesis disorders, an example of which is Zellweger syndrome. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.891

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX13	NM_002618.4	c.383G>A	p.Gly128Asp	missense_variant	Exon 2 of 4	ENST00000295030.6	NP_002609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX13	ENST00000295030.6	c.383G>A	p.Gly128Asp	missense_variant	Exon 2 of 4	1	NM_002618.4	ENSP00000295030.4
PEX13	ENST00000472678.1	n.446G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461890 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

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: 0.00000180

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	0.74
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.053	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	0.22	D
MutationAssessor	Uncertain	2.7	M
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-2.3	N
REVEL	Pathogenic	0.73
Sift	Uncertain	0.017	D
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.92
MutPred		0.68		Loss of helix (P = 0.0376);
MVP		0.87
MPC		0.52
ClinPred		0.89	D
GERP RS		5.8
Varity_R		0.74
gMVP		0.95

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: chr2-61258844;