rs150005994

Variant names:

• chr7-92489923-ATT-A
• rs150005994
• NM_000466.3:c.3439-14_3439-13delAA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000466.3(PEX1):​c.3439-14_3439-13delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0338 in 1,608,206 control chromosomes in the GnomAD database, including 1,057 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (56 hom., cov: 32)
  • Exomes 𝑓: 0.035 (1001 hom.)
• Consequence: PEX1 NM_000466.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.576
• Publications: 3 publications found

Genes affected

PEX1 (HGNC:8850): (peroxisomal biogenesis factor 1) This gene encodes a member of the AAA ATPase family, a large group of ATPases associated with diverse cellular activities. This protein is cytoplasmic but is often anchored to a peroxisomal membrane where it forms a heteromeric complex and plays a role in the import of proteins into peroxisomes and peroxisome biogenesis. Mutations in this gene have been associated with complementation group 1 peroxisomal disorders such as neonatal adrenoleukodystrophy, infantile Refsum disease, and Zellweger syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2013]

ENSG00000244055 (HGNC:):

GATAD1 (HGNC:29941): (GATA zinc finger domain containing 1) The protein encoded by this gene contains a zinc finger at the N-terminus, and is thought to bind to a histone modification site that regulates gene expression. Mutations in this gene have been associated with autosomal recessive dilated cardiomyopathy. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2012]

GATAD1 Gene-Disease associations (from GenCC):

• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• dilated cardiomyopathy 2B

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 7-92489923-ATT-A is Benign according to our data. Variant chr7-92489923-ATT-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 256220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX1	NM_000466.3	c.3439-14_3439-13delAA		intron_variant	Intron 21 of 23	ENST00000248633.9	NP_000457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX1	ENST00000248633.9	c.3439-14_3439-13delAA		intron_variant	Intron 21 of 23	1	NM_000466.3	ENSP00000248633.4

Frequencies

GnomAD3 genomes AF: 0.0253 AC: 3846 AN: 152188 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.00705

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0216

Gnomad ASJ AF: 0.0375

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0182

Gnomad FIN AF: 0.0221

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0386

Gnomad OTH AF: 0.0301

GnomAD2 exomes AF: 0.0270 AC: 6737 AN: 249814 AF XY: 0.0282

Gnomad AFR exome AF: 0.00618

Gnomad AMR exome AF: 0.0147

Gnomad ASJ exome AF: 0.0425

Gnomad EAS exome AF: 0.00365

Gnomad FIN exome AF: 0.0235

Gnomad NFE exome AF: 0.0380

Gnomad OTH exome AF: 0.0330

GnomAD4 exome AF: 0.0347 AC: 50466 AN: 1455900 Hom.: 1001 AF XY: 0.0345 AC XY: 25035 AN XY: 724772

African (AFR) AF: 0.00626 AC: 209 AN: 33368

American (AMR) AF: 0.0160 AC: 714 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.0402 AC: 1048 AN: 26098

East Asian (EAS) AF: 0.00313 AC: 124 AN: 39672

South Asian (SAS) AF: 0.0213 AC: 1835 AN: 86082

European-Finnish (FIN) AF: 0.0221 AC: 1180 AN: 53380

Middle Eastern (MID) AF: 0.0618 AC: 355 AN: 5744

European-Non Finnish (NFE) AF: 0.0388 AC: 42925 AN: 1106702

Other (OTH) AF: 0.0345 AC: 2076 AN: 60172

GnomAD4 genome AF: 0.0252 AC: 3843 AN: 152306 Hom.: 56 Cov.: 32 AF XY: 0.0245 AC XY: 1821 AN XY: 74468

African (AFR) AF: 0.00702 AC: 292 AN: 41566

American (AMR) AF: 0.0216 AC: 330 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0375 AC: 130 AN: 3468

East Asian (EAS) AF: 0.00367 AC: 19 AN: 5184

South Asian (SAS) AF: 0.0186 AC: 90 AN: 4830

European-Finnish (FIN) AF: 0.0221 AC: 234 AN: 10608

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0385 AC: 2620 AN: 68026

Other (OTH) AF: 0.0298 AC: 63 AN: 2116

Alfa AF: 0.0332 Hom.: 17

Bravo AF: 0.0258

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Zellweger spectrum disorders Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Apr 11, 2018

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

not provided Benign:1

Oct 18, 2023

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria.

Peroxisome biogenesis disorder 1A (Zellweger) Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.58
Mutation Taster		=20/80	disease causing

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: rs150005994; hg19: chr7-92119237;