NM_018622.7:c.512-162T>G

Variant names:

• chr3-183844488-A-C
• rs3811725
• NM_018622.7:c.512-162T>G

Variant summary

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

The NM_018622.7(PARL):​c.512-162T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 621,298 control chromosomes in the GnomAD database, including 65,056 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 0.42 (14020 hom., cov: 32)
  • Exomes 𝑓: 0.46 (51036 hom.)
• Consequence: PARL NM_018622.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640
• Publications: 15 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018622.7. 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.512-162T>G		intron	N/A	NP_061092.3
	PARL	NM_001324436.2		c.512-162T>G		intron	N/A	NP_001311365.1
	PARL	NM_001037639.3		c.512-162T>G		intron	N/A	NP_001032728.1	Q9H300-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PARL	ENST00000317096.9	TSL:1 MANE Select	c.512-162T>G		intron	N/A	ENSP00000325421.5	Q9H300-1
	ENSG00000283765	ENST00000639401.1	TSL:5	c.512-162T>G		intron	N/A	ENSP00000491227.1	A0A1W2PP11
	PARL	ENST00000311101.9	TSL:1	c.512-162T>G		intron	N/A	ENSP00000310676.5	Q9H300-2

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64120 AN: 151948 Hom.: 14020 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.455

GnomAD4 exome AF: 0.462 AC: 216643 AN: 469232 Hom.: 51036 Cov.: 4 AF XY: 0.461 AC XY: 116192 AN XY: 251952

African (AFR) AF: 0.316 AC: 4028 AN: 12746

American (AMR) AF: 0.511 AC: 11415 AN: 22334

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 7983 AN: 14698

East Asian (EAS) AF: 0.456 AC: 13654 AN: 29966

South Asian (SAS) AF: 0.421 AC: 19620 AN: 46638

European-Finnish (FIN) AF: 0.347 AC: 12944 AN: 37256

Middle Eastern (MID) AF: 0.570 AC: 1242 AN: 2178

European-Non Finnish (NFE) AF: 0.482 AC: 133694 AN: 277362

Other (OTH) AF: 0.463 AC: 12063 AN: 26054

GnomAD4 genome AF: 0.422 AC: 64125 AN: 152066 Hom.: 14020 Cov.: 32 AF XY: 0.416 AC XY: 30903 AN XY: 74344

African (AFR) AF: 0.314 AC: 13031 AN: 41454

American (AMR) AF: 0.483 AC: 7382 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1921 AN: 3470

East Asian (EAS) AF: 0.420 AC: 2172 AN: 5170

South Asian (SAS) AF: 0.419 AC: 2019 AN: 4820

European-Finnish (FIN) AF: 0.324 AC: 3431 AN: 10592

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32785 AN: 67970

Other (OTH) AF: 0.449 AC: 949 AN: 2112

Alfa AF: 0.472 Hom.: 55268

Bravo AF: 0.434

Asia WGS AF: 0.406 AC: 1413 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.74
DANN	Benign	0.83
PhyloP100		-0.64
PromoterAI		0.013	Neutral
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: rs3811725; hg19: chr3-183562276;