rs950397917

Variant names:

• chr2-61017767-C-A
• rs950397917
• NM_002618.4:c.8C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-61017767-C-A
• chr2-61017767-C-G
• chr2-61017767-C-T

Variant summary

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

The NM_002618.4(PEX13):​c.8C>A​(p.Ser3Tyr) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PEX13 NM_002618.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74

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]

PUS10 (HGNC:26505): (pseudouridine synthase 10) Pseudouridination, the isomerization of uridine to pseudouridine, is the most common posttranscriptional nucleotide modification found in RNA and is essential for biologic functions such as spliceosome biogenesis. Pseudouridylate synthases, such as PUS10, catalyze pseudouridination of structural RNAs, including transfer, ribosomal, and splicing RNAs. These enzymes also act as RNA chaperones, facilitating the correct folding and assembly of tRNAs (McCleverty et al., 2007 [PubMed 17900615]).[supplied by OMIM, May 2009]

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=0.34101176).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX13	NM_002618.4	c.8C>A	p.Ser3Tyr	missense_variant	Exon 1 of 4	ENST00000295030.6	NP_002609.1
PUS10	NM_144709.4	c.-16+241G>T		intron_variant	Intron 1 of 17	ENST00000316752.11	NP_653310.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX13	ENST00000295030.6	c.8C>A	p.Ser3Tyr	missense_variant	Exon 1 of 4	1	NM_002618.4	ENSP00000295030.4
PUS10	ENST00000316752.11	c.-16+241G>T		intron_variant	Intron 1 of 17	1	NM_144709.4	ENSP00000326003.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.37	.;T;T;T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.55	T;T;T;T
M_CAP	Pathogenic	0.40	D
MetaRNN	Benign	0.34	T;T;T;T
MetaSVM	Uncertain	-0.036	T
MutationAssessor	Benign	0.97	.;.;L;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-4.0	D;D;N;D
REVEL	Uncertain	0.40
Sift	Pathogenic	0.0	.;.;D;.
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.99	.;.;D;.
Vest4		0.25
MutPred		0.31		Loss of glycosylation at S3 (P = 0.004);Loss of glycosylation at S3 (P = 0.004);Loss of glycosylation at S3 (P = 0.004);Loss of glycosylation at S3 (P = 0.004);
MVP		0.80
MPC		0.27
ClinPred		1.0	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.42
gMVP		0.51

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: rs950397917; hg19: chr2-61244902;