1-10629885-G-T

Variant names:

• chr1-10629885-G-T
• rs11539794
• NM_004565.3:c.1032G>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.1032G>T​(p.Gly344Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,612,824 control chromosomes in the GnomAD database, including 25,665 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G344G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.13 (1740 hom., cov: 31)
  • Exomes 𝑓: 0.18 (23925 hom.)
• Consequence: PEX14 NM_004565.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.183
• Publications: 11 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, G2P, 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=-0.57).
• BP6: Variant 1-10629885-G-T is Benign according to our data. Variant chr1-10629885-G-T is described in ClinVar as Benign. ClinVar VariationId is 167454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.183 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 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.1032G>T	p.Gly344Gly	synonymous	Exon 9 of 9	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.1032G>T	p.Gly344Gly	synonymous	Exon 9 of 9	ENSP00000349016.4	O75381-1
	PEX14	ENST00000889280.1		c.1029G>T	p.Gly343Gly	synonymous	Exon 9 of 9	ENSP00000559339.1
	PEX14	ENST00000923290.1		c.984G>T	p.Gly328Gly	synonymous	Exon 8 of 8	ENSP00000593349.1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20464 AN: 151780 Hom.: 1740 Cov.: 31

Gnomad AFR AF: 0.0428

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0236

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.149

GnomAD2 exomes AF: 0.154 AC: 38361 AN: 249532 AF XY: 0.162

Gnomad AFR exome AF: 0.0389

Gnomad AMR exome AF: 0.0884

Gnomad ASJ exome AF: 0.203

Gnomad EAS exome AF: 0.0173

Gnomad FIN exome AF: 0.188

Gnomad NFE exome AF: 0.188

Gnomad OTH exome AF: 0.185

GnomAD4 exome AF: 0.177 AC: 258579 AN: 1460924 Hom.: 23925 Cov.: 33 AF XY: 0.178 AC XY: 129462 AN XY: 726760

African (AFR) AF: 0.0373 AC: 1250 AN: 33472

American (AMR) AF: 0.0934 AC: 4172 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 5353 AN: 26112

East Asian (EAS) AF: 0.0368 AC: 1459 AN: 39682

South Asian (SAS) AF: 0.199 AC: 17172 AN: 86180

European-Finnish (FIN) AF: 0.186 AC: 9931 AN: 53288

Middle Eastern (MID) AF: 0.226 AC: 1298 AN: 5740

European-Non Finnish (NFE) AF: 0.187 AC: 207524 AN: 1111420

Other (OTH) AF: 0.173 AC: 10420 AN: 60354

GnomAD4 genome AF: 0.135 AC: 20465 AN: 151900 Hom.: 1740 Cov.: 31 AF XY: 0.135 AC XY: 10047 AN XY: 74218

African (AFR) AF: 0.0427 AC: 1771 AN: 41438

American (AMR) AF: 0.116 AC: 1776 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 692 AN: 3470

East Asian (EAS) AF: 0.0239 AC: 123 AN: 5154

South Asian (SAS) AF: 0.179 AC: 863 AN: 4808

European-Finnish (FIN) AF: 0.193 AC: 2042 AN: 10572

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12663 AN: 67890

Other (OTH) AF: 0.147 AC: 309 AN: 2102

Alfa AF: 0.163 Hom.: 1057

Bravo AF: 0.126

Asia WGS AF: 0.103 AC: 356 AN: 3474

EpiCase AF: 0.192

EpiControl AF: 0.192

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	5.3
DANN	Benign	0.68
PhyloP100		0.18
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.9
Mutation Taster		=93/7	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: rs11539794; hg19: chr1-10689942; COSMIC: COSV108172663;