rs752610316

Variant names:

• chr3-183866738-C-A
• rs752610316
• NM_018622.7:c.349G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-183866738-C-A
• chr3-183866738-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018622.7(PARL):​c.349G>T​(p.Ala117Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A117T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PARL NM_018622.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.23
• Publications: 0 publications found

Genes affected

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]

ENSG00000283765 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARL	NM_018622.7	c.349G>T	p.Ala117Ser	missense_variant	Exon 3 of 10	ENST00000317096.9	NP_061092.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARL	ENST00000317096.9	c.349G>T	p.Ala117Ser	missense_variant	Exon 3 of 10	1	NM_018622.7	ENSP00000325421.5
ENSG00000283765	ENST00000639401.1	c.349G>T	p.Ala117Ser	missense_variant	Exon 3 of 11	5		ENSP00000491227.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.066	.;T;.;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Uncertain	0.094	D
MetaRNN	Uncertain	0.53	D;D;D;D
MetaSVM	Uncertain	0.024	D
MutationAssessor	Uncertain	2.4	.;M;M;.
PhyloP100		7.2
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.7	.;N;N;N
REVEL	Uncertain	0.40
Sift	Benign	0.083	.;T;T;T
Sift4G	Benign	0.25	.;T;T;T
Polyphen		0.74, 1.0	.;P;D;.
Vest4		0.69, 0.75, 0.72
MutPred		0.46		Gain of disorder (P = 0.0793);Gain of disorder (P = 0.0793);Gain of disorder (P = 0.0793);Gain of disorder (P = 0.0793);
MVP		0.96
MPC		0.15
ClinPred		0.94	D
GERP RS		5.3
Varity_R		0.27
gMVP		0.71
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs752610316; hg19: chr3-183584526;