chr1-10474973-TC-AG

Variant names:

• chr1-10474973-TC-AG
• NM_004565.3:c.7_8delTCinsAG
• PEX14 p.4

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_004565.3(PEX14):​c.7_8delTCinsAG​(p.4) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S3S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PEX14 NM_004565.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.72
• Publications: 0 publications found

Genes affected

PEX14 (HGNC:8856): (peroxisomal biogenesis factor 14) This gene encodes an essential component of the peroxisomal import machinery. The protein is integrated into peroxisome membranes with its C-terminus exposed to the cytosol, and interacts with the cytosolic receptor for proteins containing a PTS1 peroxisomal targeting signal. The protein also functions as a transcriptional corepressor and interacts with a histone deacetylase. A mutation in this gene results in one form of Zellweger syndrome. [provided by RefSeq, Jul 2008]

PEX14 Gene-Disease associations (from GenCC):

• peroxisome biogenesis disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• peroxisome biogenesis disorder 13A (Zellweger)

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• Zellweger spectrum disorders

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004565.3. 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
	PEX14	NM_004565.3	MANE Select	c.7_8delTCinsAG	p.4	synonymous	N/A	NP_004556.1	O75381-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX14	ENST00000356607.9	TSL:1 MANE Select	c.7_8delTCinsAG	p.4	synonymous	N/A	ENSP00000349016.4	O75381-1
	PEX14	ENST00000889280.1		c.7_8delTCinsAG	p.4	synonymous	N/A	ENSP00000559339.1
	PEX14	ENST00000923290.1		c.7_8delTCinsAG	p.4	synonymous	N/A	ENSP00000593349.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-10535030;