Genetic Variant ENSG00000293259:n.114A>T (chr3-183885037-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000445165.2(ENSG00000293259):n.114A>T 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 0.0000012 in 831,598 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 0.0000012 ( 0 hom. )

Consequence

ENSG00000293259
ENST00000445165.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.75

Publications

0 publications found

Variant links:

Genes affected

ENSG00000293259 (HGNC:):

ENSG00000293259 links:

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]

PARL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARL	NM_018622.7 link	c.-191T>A		upstream_gene_variant		ENST00000317096.9	NP_061092.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARL	ENST00000317096.9 link	c.-191T>A		upstream_gene_variant		1	NM_018622.7	ENSP00000325421.5
ENSG00000283765	ENST00000639401.1 link	c.-191T>A		upstream_gene_variant		5		ENSP00000491227.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000120

AC:

AN:

831598

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

420360

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21000

American (AMR)

AF:

0.00

AC:

AN:

29042

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18150

East Asian (EAS)

AF:

0.00

AC:

AN:

32646

South Asian (SAS)

AF:

0.00

AC:

AN:

59748

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30988

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2802

European-Non Finnish (NFE)

AF:

0.00000167

AC:

AN:

598368

Other (OTH)

AF:

0.00

AC:

AN:

38854

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.29

(source)

DANN

Benign

0.59

PhyloP100

-4.8

PromoterAI

-0.023

Neutral

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over