rs41274482

Variant names:

• chr1-10599281-C-G
• rs41274482
• NM_004565.3:c.213C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-10599281-C-G
• chr1-10599281-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_004565.3(PEX14):​c.213C>G​(p.Gly71Gly) variant causes a synonymous change. The variant allele was found at a frequency of 0.0153 in 1,613,366 control chromosomes in the GnomAD database, including 294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0097 (24 hom., cov: 33)
  • Exomes 𝑓: 0.016 (270 hom.)
• Consequence: PEX14 NM_004565.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 4.21
• Publications: 3 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

ENSG00000307253 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 1-10599281-C-G is Benign according to our data. Variant chr1-10599281-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 259435.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00968 (1474/152324) while in subpopulation NFE AF = 0.0159 (1084/68036). AF 95% confidence interval is 0.0151. There are 24 homozygotes in GnomAd4. There are 668 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 24 AR gene

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.213C>G	p.Gly71Gly	synonymous	Exon 4 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.213C>G	p.Gly71Gly	synonymous	Exon 4 of 9	ENSP00000349016.4	O75381-1
	PEX14	ENST00000889280.1		c.213C>G	p.Gly71Gly	synonymous	Exon 4 of 9	ENSP00000559339.1
	PEX14	ENST00000923290.1		c.165C>G	p.Gly55Gly	synonymous	Exon 3 of 8	ENSP00000593349.1

Frequencies

GnomAD3 genomes AF: 0.00968 AC: 1474 AN: 152206 Hom.: 24 Cov.: 33

Gnomad AFR AF: 0.00265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00433

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0159

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00899 AC: 2260 AN: 251444 AF XY: 0.00918

Gnomad AFR exome AF: 0.00314

Gnomad AMR exome AF: 0.00682

Gnomad ASJ exome AF: 0.00774

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00508

Gnomad NFE exome AF: 0.0151

Gnomad OTH exome AF: 0.00945

GnomAD4 exome AF: 0.0159 AC: 23175 AN: 1461042 Hom.: 270 Cov.: 32 AF XY: 0.0152 AC XY: 11060 AN XY: 726872

African (AFR) AF: 0.00296 AC: 99 AN: 33460

American (AMR) AF: 0.00678 AC: 303 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00872 AC: 228 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86248

European-Finnish (FIN) AF: 0.00584 AC: 312 AN: 53420

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5768

European-Non Finnish (NFE) AF: 0.0192 AC: 21332 AN: 1111230

Other (OTH) AF: 0.0144 AC: 869 AN: 60364

GnomAD4 genome AF: 0.00968 AC: 1474 AN: 152324 Hom.: 24 Cov.: 33 AF XY: 0.00897 AC XY: 668 AN XY: 74488

African (AFR) AF: 0.00265 AC: 110 AN: 41566

American (AMR) AF: 0.0116 AC: 177 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00433 AC: 46 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0159 AC: 1084 AN: 68036

Other (OTH) AF: 0.00994 AC: 21 AN: 2112

Alfa AF: 0.0101 Hom.: 0

Bravo AF: 0.0103

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0164

EpiControl AF: 0.0155

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	10
DANN	Benign	0.81
PhyloP100		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs41274482; hg19: chr1-10659338; COSMIC: COSV100750215;