chr22-18078385-C-T

Variant names:

• chr22-18078385-C-T
• rs984532105
• NM_001127649.3:c.9C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6 BP7

The NM_001127649.3(PEX26):​c.9C>T​(p.Ser3Ser) 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 (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PEX26 NM_001127649.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.216
• Publications: 0 publications found

Genes affected

PEX26 (HGNC:22965): (peroxisomal biogenesis factor 26) This gene belongs to the peroxin-26 gene family. It is probably required for protein import into peroxisomes. It anchors PEX1 and PEX6 to peroxisome membranes, possibly to form heteromeric AAA ATPase complexes required for the import of proteins into peroxisomes. Defects in this gene are the cause of peroxisome biogenesis disorder complementation group 8 (PBD-CG8). PBD refers to a group of peroxisomal disorders arising from a failure of protein import into the peroxisomal membrane or matrix. The PBD group is comprised of four disorders: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Dec 2010]

PEX26 Gene-Disease associations (from GenCC):

• peroxisome biogenesis disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• peroxisome biogenesis disorder 7A (Zellweger)

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• peroxisome biogenesis disorder 7B

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P
• Zellweger spectrum disorders

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000288683 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 22-18078385-C-T is Benign according to our data. Variant chr22-18078385-C-T is described in CliVar as Likely_benign. Clinvar id is 3048331.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr22-18078385-C-T is described in CliVar as Likely_benign. Clinvar id is 3048331.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr22-18078385-C-T is described in CliVar as Likely_benign. Clinvar id is 3048331.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr22-18078385-C-T is described in CliVar as Likely_benign. Clinvar id is 3048331.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr22-18078385-C-T is described in CliVar as Likely_benign. Clinvar id is 3048331.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr22-18078385-C-T is described in CliVar as Likely_benign. Clinvar id is 3048331.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr22-18078385-C-T is described in CliVar as Likely_benign. Clinvar id is 3048331.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr22-18078385-C-T is described in CliVar as Likely_benign. Clinvar id is 3048331.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.216 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX26	NM_001127649.3	c.9C>T	p.Ser3Ser	synonymous_variant	Exon 1 of 5	ENST00000399744.8	NP_001121121.1
PEX26	NM_017929.6	c.9C>T	p.Ser3Ser	synonymous_variant	Exon 2 of 6		NP_060399.1
PEX26	NM_001199319.2	c.9C>T	p.Ser3Ser	synonymous_variant	Exon 2 of 5		NP_001186248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX26	ENST00000399744.8	c.9C>T	p.Ser3Ser	synonymous_variant	Exon 1 of 5	1	NM_001127649.3	ENSP00000382648.4
ENSG00000288683	ENST00000474897.6	n.9C>T		non_coding_transcript_exon_variant	Exon 2 of 9	5		ENSP00000434235.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1447506 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 719576

African (AFR) AF: 0.00 AC: 0 AN: 33260

American (AMR) AF: 0.00 AC: 0 AN: 43546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25904

East Asian (EAS) AF: 0.00 AC: 0 AN: 39402

South Asian (SAS) AF: 0.00 AC: 0 AN: 84680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48788

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106276

Other (OTH) AF: 0.00 AC: 0 AN: 59888

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

PEX26-related disorder Benign:1

Mar 03, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	13
DANN	Benign	0.88
PhyloP100		0.22
PromoterAI		-0.025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs984532105; hg19: chr22-18561151;