rs34825053

Variant names:

• chr7-92489340-G-A
• rs34825053
• NM_000466.3:c.3720C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-92489340-G-A
• chr7-92489340-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000466.3(PEX1):​c.3720C>T​(p.His1240His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000926 in 1,613,068 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0053 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00047 (7 hom.)
• Consequence: PEX1 NM_000466.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.800
• Publications: 1 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: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 7-92489340-G-A is Benign according to our data. Variant chr7-92489340-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 256222.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.8 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00529 (806/152280) while in subpopulation AFR AF = 0.0178 (740/41552). AF 95% confidence interval is 0.0167. There are 5 homozygotes in GnomAd4. There are 377 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000466.3. 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
	PEX1	NM_000466.3	MANE Select	c.3720C>T	p.His1240His	synonymous	Exon 23 of 24	NP_000457.1	O43933-1
	PEX1	NM_001282677.2		c.3549C>T	p.His1183His	synonymous	Exon 22 of 23	NP_001269606.1	A0A0C4DG33
	PEX1	NM_001282678.2		c.3096C>T	p.His1032His	synonymous	Exon 23 of 24	NP_001269607.1	B4DER6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX1	ENST00000248633.9	TSL:1 MANE Select	c.3720C>T	p.His1240His	synonymous	Exon 23 of 24	ENSP00000248633.4	O43933-1
	PEX1	ENST00000428214.5	TSL:1	c.3549C>T	p.His1183His	synonymous	Exon 22 of 23	ENSP00000394413.1	A0A0C4DG33
	PEX1	ENST00000951788.1		c.3774C>T	p.His1258His	synonymous	Exon 23 of 24	ENSP00000621847.1

Frequencies

GnomAD3 genomes AF: 0.00527 AC: 802 AN: 152162 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00126 AC: 317 AN: 250844 AF XY: 0.000893

Gnomad AFR exome AF: 0.0167

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.000471 AC: 688 AN: 1460788 Hom.: 7 Cov.: 30 AF XY: 0.000407 AC XY: 296 AN XY: 726768

African (AFR) AF: 0.0171 AC: 571 AN: 33456

American (AMR) AF: 0.00119 AC: 53 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53366

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111152

Other (OTH) AF: 0.000895 AC: 54 AN: 60354

GnomAD4 genome AF: 0.00529 AC: 806 AN: 152280 Hom.: 5 Cov.: 32 AF XY: 0.00506 AC XY: 377 AN XY: 74460

African (AFR) AF: 0.0178 AC: 740 AN: 41552

American (AMR) AF: 0.00301 AC: 46 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68028

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00234 Hom.: 7

Bravo AF: 0.00581

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	2	Zellweger spectrum disorders (2)
-	-	1	not provided (1)
-	-	1	Peroxisome biogenesis disorder 1A (Zellweger) (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	5.3
DANN	Benign	0.71
PhyloP100		0.80
Mutation Taster		=100/0	polymorphism

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: rs34825053; hg19: chr7-92118654; COSMIC: COSV104373594;