chr2-61017768-C-G

Variant names:

• chr2-61017768-C-G
• rs745465894
• NM_002618.4:c.9C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_002618.4(PEX13):​c.9C>G​(p.Ser3Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000573 in 1,397,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. S3S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: PEX13 NM_002618.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.806
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 2-61017768-C-G is Benign according to our data. Variant chr2-61017768-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1572021.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.806 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002618.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX13	NM_002618.4	MANE Select	c.9C>G	p.Ser3Ser	synonymous	Exon 1 of 4	NP_002609.1	Q92968
	PUS10	NM_144709.4	MANE Select	c.-16+240G>C		intron	N/A	NP_653310.2	Q3MIT2
	PUS10	NM_001322127.1		c.-623+240G>C		intron	N/A	NP_001309056.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX13	ENST00000295030.6	TSL:1 MANE Select	c.9C>G	p.Ser3Ser	synonymous	Exon 1 of 4	ENSP00000295030.4	Q92968
	PEX13	ENST00000444100.2	TSL:1	c.9C>G	p.Ser3Ser	synonymous	Exon 1 of 2	ENSP00000405184.2	D3YTD3
	PEX13	ENST00000414712.2	TSL:1	c.9C>G	p.Ser3Ser	synonymous	Exon 1 of 2	ENSP00000405413.2	G5E9N6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000573 AC: 8 AN: 1397214 Hom.: 0 Cov.: 31 AF XY: 0.00000871 AC XY: 6 AN XY: 689042

African (AFR) AF: 0.00 AC: 0 AN: 31570

American (AMR) AF: 0.00 AC: 0 AN: 35616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25166

East Asian (EAS) AF: 0.00 AC: 0 AN: 35864

South Asian (SAS) AF: 0.00 AC: 0 AN: 79084

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48114

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5340

European-Non Finnish (NFE) AF: 0.00000742 AC: 8 AN: 1078566

Other (OTH) AF: 0.00 AC: 0 AN: 57894

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Peroxisome biogenesis disorder 11A (Zellweger) (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.5
DANN	Benign	0.62
PhyloP100		-0.81
PromoterAI		0.097	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs745465894; hg19: chr2-61244903;