chr17-35574898-TTAAG-T

Position:

• chr17-35574898-TTAAG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000225873.9(PEX12):​c.*880_*883del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,088 control chromosomes in the GnomAD database, including 17,258 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (17196 hom., cov: 0)
  • Exomes 𝑓: 0.54 (62 hom.)
• Consequence: PEX12 ENST00000225873.9 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.82

Genes affected

PEX12 (HGNC:8854): (peroxisomal biogenesis factor 12) This gene belongs to the peroxin-12 family. Peroxins (PEXs) are proteins that are essential for the assembly of functional peroxisomes. The peroxisome biogenesis disorders (PBDs) are a group of genetically heterogeneous autosomal recessive, lethal diseases characterized by multiple defects in peroxisome function. The peroxisomal biogenesis disorders are a heterogeneous group with at least 14 complementation groups and with more than 1 phenotype being observed in cases falling into particular complementation groups. Although the clinical features of PBD patients vary, cells from all PBD patients exhibit a defect in the import of one or more classes of peroxisomal matrix proteins into the organelle. Defects in this gene are a cause of Zellweger syndrome (ZWS). [provided by RefSeq, Oct 2008]

SNHG30 (HGNC:52836): (small nucleolar RNA host gene 30)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 17-35574898-TTAAG-T is Benign according to our data. Variant chr17-35574898-TTAAG-T is described in ClinVar as [Benign]. Clinvar id is 322635.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX12	NM_000286.3	c.*880_*883del		3_prime_UTR_variant	3/3	ENST00000225873.9	NP_000277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX12	ENST00000225873.9	c.*880_*883del		3_prime_UTR_variant	3/3	1	NM_000286.3	ENSP00000225873	P1
SNHG30	ENST00000659685.1			non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72177 AN: 151540 Hom.: 17203 Cov.: 0

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.462

GnomAD4 exome AF: 0.544 AC: 234 AN: 430 Hom.: 62 AF XY: 0.554 AC XY: 143 AN XY: 258

Gnomad4 FIN exome AF: 0.545

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.476 AC: 72183 AN: 151658 Hom.: 17196 Cov.: 0 AF XY: 0.478 AC XY: 35459 AN XY: 74110

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.373

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.458

Alfa AF: 0.495 Hom.: 2270

Bravo AF: 0.472

Asia WGS AF: 0.457 AC: 1584 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Peroxisome biogenesis disorder 1A (Zellweger) Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs35050283; hg19: chr17-33901917;