rs10068

Variant names:

• chr17-35574946-C-G
• rs10068
• NM_000286.3:c.*836G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000286.3(PEX12):​c.*836G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 152,472 control chromosomes in the GnomAD database, including 10,385 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10367 hom., cov: 32)
  • Exomes 𝑓: 0.33 (18 hom.)
• Consequence: PEX12 NM_000286.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.516
• Publications: 9 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 17-35574946-C-G is Benign according to our data. Variant chr17-35574946-C-G is described in ClinVar as Benign. ClinVar VariationId is 322636.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000286.3. 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
	PEX12	NM_000286.3	MANE Select	c.*836G>C		3_prime_UTR	Exon 3 of 3	NP_000277.1	O00623

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX12	ENST00000225873.9	TSL:1 MANE Select	c.*836G>C		3_prime_UTR	Exon 3 of 3	ENSP00000225873.3	O00623
	SNHG30	ENST00000592381.1	TSL:2	n.*154C>G		downstream_gene	N/A
	SNHG30	ENST00000638682.1	TSL:5	n.*103C>G		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55958 AN: 151924 Hom.: 10343 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.392

GnomAD4 exome AF: 0.328 AC: 141 AN: 430 Hom.: 18 Cov.: 0 AF XY: 0.333 AC XY: 86 AN XY: 258

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.325 AC: 138 AN: 424

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.369 AC: 56045 AN: 152042 Hom.: 10367 Cov.: 32 AF XY: 0.369 AC XY: 27442 AN XY: 74318

African (AFR) AF: 0.379 AC: 15705 AN: 41458

American (AMR) AF: 0.380 AC: 5803 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1679 AN: 3472

East Asian (EAS) AF: 0.367 AC: 1900 AN: 5180

South Asian (SAS) AF: 0.454 AC: 2186 AN: 4818

European-Finnish (FIN) AF: 0.350 AC: 3687 AN: 10548

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23777 AN: 67980

Other (OTH) AF: 0.397 AC: 839 AN: 2114

Alfa AF: 0.358 Hom.: 1303

Bravo AF: 0.374

Asia WGS AF: 0.441 AC: 1535 AN: 3474

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Peroxisome biogenesis disorder 3A (Zellweger) (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.5
DANN	Benign	0.78
PhyloP100		-0.52
Mutation Taster		=100/0	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: rs10068; hg19: chr17-33901965;