3-183885043-C-G

Variant names:

• chr3-183885043-C-G
• rs3792588
• ENST00000445165.2:n.120C>G

Variant summary

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

The ENST00000445165.2(ENSG00000293259):​n.120C>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 0.145 in 945,084 control chromosomes in the GnomAD database, including 13,430 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 (1844 hom., cov: 33)
  • Exomes 𝑓: 0.15 (11586 hom.)
• Consequence: ENSG00000293259 ENST00000445165.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.25
• Publications: 4 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARL	NM_018622.7	MANE Select	c.-197G>C		upstream_gene	N/A	NP_061092.3
	PARL	NM_001324436.2		c.-197G>C		upstream_gene	N/A	NP_001311365.1
	PARL	NM_001037639.3		c.-197G>C		upstream_gene	N/A	NP_001032728.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000293259	ENST00000445165.2	TSL:2	n.120C>G		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000293259	ENST00000833400.1		n.7C>G		non_coding_transcript_exon	Exon 1 of 2
	PARL	ENST00000317096.9	TSL:1 MANE Select	c.-197G>C		upstream_gene	N/A	ENSP00000325421.5

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19392 AN: 152066 Hom.: 1830 Cov.: 33

Gnomad AFR AF: 0.0341

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.0926

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.148 AC: 117593 AN: 792900 Hom.: 11586 Cov.: 10 AF XY: 0.151 AC XY: 60754 AN XY: 401532

African (AFR) AF: 0.0303 AC: 609 AN: 20104

American (AMR) AF: 0.232 AC: 6464 AN: 27840

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 1752 AN: 17522

East Asian (EAS) AF: 0.456 AC: 14805 AN: 32434

South Asian (SAS) AF: 0.245 AC: 14251 AN: 58122

European-Finnish (FIN) AF: 0.195 AC: 5980 AN: 30664

Middle Eastern (MID) AF: 0.0990 AC: 266 AN: 2688

European-Non Finnish (NFE) AF: 0.120 AC: 67859 AN: 565952

Other (OTH) AF: 0.149 AC: 5607 AN: 37574

GnomAD4 genome AF: 0.128 AC: 19420 AN: 152184 Hom.: 1844 Cov.: 33 AF XY: 0.135 AC XY: 10050 AN XY: 74398

African (AFR) AF: 0.0342 AC: 1420 AN: 41568

American (AMR) AF: 0.195 AC: 2984 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0926 AC: 321 AN: 3466

East Asian (EAS) AF: 0.451 AC: 2312 AN: 5128

South Asian (SAS) AF: 0.255 AC: 1232 AN: 4824

European-Finnish (FIN) AF: 0.197 AC: 2086 AN: 10596

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

European-Non Finnish (NFE) AF: 0.126 AC: 8549 AN: 67998

Other (OTH) AF: 0.137 AC: 290 AN: 2114

Alfa AF: 0.118 Hom.: 155

Bravo AF: 0.122

Asia WGS AF: 0.359 AC: 1247 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	0.52
DANN	Benign	0.49
PhyloP100		-2.3
PromoterAI		0.081	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3792588; hg19: chr3-183602831; COSMIC: COSV57699844;