3-183885037-A-G

Variant names:

• chr3-183885037-A-G
• rs3792589
• ENST00000445165.2:n.114A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000445165.2(ENSG00000293259):​n.114A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 982,496 control chromosomes in the GnomAD database, including 13,790 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1852 hom., cov: 33)
  • Exomes 𝑓: 0.15 (11938 hom.)
• Consequence: ENSG00000293259 ENST00000445165.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.75
• Publications: 5 publications found

Genes affected

ENSG00000293259 (HGNC:):

PARL (HGNC:18253): (presenilin associated rhomboid like) This gene encodes a member of the rhomboid family of intramembrane serine proteases that is localized to the inner mitochondrial membrane. The encoded protein regulates mitochondrial remodeling and apoptosis through regulated substrate proteolysis. Proteolytic processing of the encoded protein results in the release of a small peptide, P-beta, which may transit to the nucleus. Mutations in this gene may be associated with Parkinson's disease. [provided by RefSeq, May 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000445165.2. 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
	PARL	NM_018622.7	MANE Select	c.-191T>C		upstream_gene	N/A	NP_061092.3
	PARL	NM_001324436.2		c.-191T>C		upstream_gene	N/A	NP_001311365.1
	PARL	NM_001037639.3		c.-191T>C		upstream_gene	N/A	NP_001032728.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000293259	ENST00000445165.2	TSL:2	n.114A>G		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000293259	ENST00000833400.1		n.1A>G		non_coding_transcript_exon	Exon 1 of 2
	PARL	ENST00000317096.9	TSL:1 MANE Select	c.-191T>C		upstream_gene	N/A	ENSP00000325421.5

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19687 AN: 151854 Hom.: 1838 Cov.: 33

Gnomad AFR AF: 0.0410

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.0943

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.130

GnomAD4 exome AF: 0.149 AC: 123965 AN: 830524 Hom.: 11938 Cov.: 11 AF XY: 0.152 AC XY: 63779 AN XY: 419834

African (AFR) AF: 0.0380 AC: 798 AN: 20990

American (AMR) AF: 0.225 AC: 6528 AN: 28972

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 1820 AN: 18124

East Asian (EAS) AF: 0.457 AC: 14915 AN: 32616

South Asian (SAS) AF: 0.244 AC: 14557 AN: 59654

European-Finnish (FIN) AF: 0.194 AC: 6020 AN: 30976

Middle Eastern (MID) AF: 0.0969 AC: 271 AN: 2798

European-Non Finnish (NFE) AF: 0.123 AC: 73214 AN: 597570

Other (OTH) AF: 0.150 AC: 5842 AN: 38824

GnomAD4 genome AF: 0.130 AC: 19714 AN: 151972 Hom.: 1852 Cov.: 33 AF XY: 0.137 AC XY: 10196 AN XY: 74280

African (AFR) AF: 0.0411 AC: 1703 AN: 41478

American (AMR) AF: 0.196 AC: 2993 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0943 AC: 327 AN: 3466

East Asian (EAS) AF: 0.450 AC: 2307 AN: 5122

South Asian (SAS) AF: 0.256 AC: 1232 AN: 4812

European-Finnish (FIN) AF: 0.197 AC: 2084 AN: 10566

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8552 AN: 67958

Other (OTH) AF: 0.139 AC: 292 AN: 2108

Alfa AF: 0.113 Hom.: 151

Bravo AF: 0.124

Asia WGS AF: 0.360 AC: 1249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.57
PhyloP100		-4.8
PromoterAI		-0.086	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3792589; hg19: chr3-183602825; COSMIC: COSV57699842;