1-10629867-C-T

Variant names:

• chr1-10629867-C-T
• rs2128414
• NM_004565.3:c.1014C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004565.3(PEX14):​c.1014C>T​(p.Asp338Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0457 in 1,611,834 control chromosomes in the GnomAD database, including 2,504 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (242 hom., cov: 32)
  • Exomes 𝑓: 0.046 (2262 hom.)
• Consequence: PEX14 NM_004565.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0630
• Publications: 9 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Zellweger spectrum disorders

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 1-10629867-C-T is Benign according to our data. Variant chr1-10629867-C-T is described in ClinVar as Benign. ClinVar VariationId is 167453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.063 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

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.1014C>T	p.Asp338Asp	synonymous	Exon 9 of 9	NP_004556.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX14	ENST00000356607.9	TSL:1 MANE Select	c.1014C>T	p.Asp338Asp	synonymous	Exon 9 of 9	ENSP00000349016.4
	PEX14	ENST00000889280.1		c.1011C>T	p.Asp337Asp	synonymous	Exon 9 of 9	ENSP00000559339.1
	PEX14	ENST00000923290.1		c.966C>T	p.Asp322Asp	synonymous	Exon 8 of 8	ENSP00000593349.1

Frequencies

GnomAD3 genomes AF: 0.0473 AC: 7178 AN: 151690 Hom.: 243 Cov.: 32

Gnomad AFR AF: 0.0553

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.0338

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0425

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0344

Gnomad OTH AF: 0.0480

GnomAD2 exomes AF: 0.0568 AC: 14144 AN: 248906 AF XY: 0.0599

Gnomad AFR exome AF: 0.0572

Gnomad AMR exome AF: 0.0303

Gnomad ASJ exome AF: 0.0310

Gnomad EAS exome AF: 0.119

Gnomad FIN exome AF: 0.0461

Gnomad NFE exome AF: 0.0368

Gnomad OTH exome AF: 0.0497

GnomAD4 exome AF: 0.0455 AC: 66439 AN: 1460026 Hom.: 2262 Cov.: 31 AF XY: 0.0480 AC XY: 34845 AN XY: 726306

African (AFR) AF: 0.0551 AC: 1843 AN: 33456

American (AMR) AF: 0.0325 AC: 1450 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.0298 AC: 777 AN: 26102

East Asian (EAS) AF: 0.124 AC: 4927 AN: 39674

South Asian (SAS) AF: 0.132 AC: 11344 AN: 86118

European-Finnish (FIN) AF: 0.0493 AC: 2626 AN: 53298

Middle Eastern (MID) AF: 0.0537 AC: 309 AN: 5758

European-Non Finnish (NFE) AF: 0.0359 AC: 39823 AN: 1110688

Other (OTH) AF: 0.0554 AC: 3340 AN: 60332

GnomAD4 genome AF: 0.0473 AC: 7174 AN: 151808 Hom.: 242 Cov.: 32 AF XY: 0.0479 AC XY: 3552 AN XY: 74178

African (AFR) AF: 0.0552 AC: 2285 AN: 41366

American (AMR) AF: 0.0338 AC: 516 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0271 AC: 94 AN: 3468

East Asian (EAS) AF: 0.126 AC: 648 AN: 5124

South Asian (SAS) AF: 0.149 AC: 713 AN: 4792

European-Finnish (FIN) AF: 0.0425 AC: 449 AN: 10568

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0343 AC: 2332 AN: 67908

Other (OTH) AF: 0.0475 AC: 100 AN: 2106

Alfa AF: 0.0381 Hom.: 51

Bravo AF: 0.0458

Asia WGS AF: 0.105 AC: 365 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Peroxisome biogenesis disorder 13A (Zellweger) (1)
-	-	1	Peroxisome biogenesis disorder, complementation group K (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	2.6
DANN	Benign	0.62
PhyloP100		-0.063
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs2128414; hg19: chr1-10689924; COSMIC: COSV63062147;