2-61031791-T-C

Variant names:

• chr2-61031791-T-C
• rs369851185
• NM_002618.4:c.465T>C

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.465T>C​(p.Tyr155Tyr) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PEX13 NM_002618.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.732
• 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]

PEX13 Gene-Disease associations (from GenCC):

• peroxisome biogenesis disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• peroxisome biogenesis disorder 11A (Zellweger)

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• peroxisome biogenesis disorder 11B

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• Zellweger spectrum disorders

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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 2-61031791-T-C is Benign according to our data. Variant chr2-61031791-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3012978.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.732 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.465T>C	p.Tyr155Tyr	synonymous	Exon 2 of 4	NP_002609.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX13	ENST00000295030.6	TSL:1 MANE Select	c.465T>C	p.Tyr155Tyr	synonymous	Exon 2 of 4	ENSP00000295030.4
	PEX13	ENST00000920043.1		c.564T>C	p.Tyr188Tyr	synonymous	Exon 3 of 5	ENSP00000590102.1
	PEX13	ENST00000902278.1		c.465T>C	p.Tyr155Tyr	synonymous	Exon 2 of 4	ENSP00000572337.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

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	5.3
DANN	Benign	0.47
PhyloP100		0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=93/7	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: rs369851185; hg19: chr2-61258926;