10-3138106-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014889.4(PITRM1):c.3039G>A(p.Lys1013=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,604,876 control chromosomes in the GnomAD database, including 59,929 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5697 hom., cov: 33)
  • Exomes 𝑓: 0.27 (54232 hom.)
• Consequence: PITRM1 NM_014889.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.24

Genes affected

PITRM1 (HGNC:17663): (pitrilysin metallopeptidase 1) The protein encoded by this gene is an ATP-dependent metalloprotease that degrades post-cleavage mitochondrial transit peptides. The encoded protein binds zinc and can also degrade amyloid beta A4 protein, suggesting a possible role in Alzheimer's disease. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 10-3138106-C-T is Benign according to our data. Variant chr10-3138106-C-T is described in ClinVar as [Benign]. Clinvar id is 1600998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.24 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PITRM1	NM_014889.4	c.3039G>A	p.Lys1013=	synonymous_variant	27/27	ENST00000224949.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PITRM1	ENST00000224949.9	c.3039G>A	p.Lys1013=	synonymous_variant	27/27	1	NM_014889.4	P3

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41203 AN: 151996 Hom.: 5696 Cov.: 33

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.288

GnomAD3 exomes AF: 0.274 AC: 65964 AN: 240588 Hom.: 9201 AF XY: 0.272 AC XY: 35419 AN XY: 130400

Gnomad AFR exome AF: 0.236

Gnomad AMR exome AF: 0.304

Gnomad ASJ exome AF: 0.371

Gnomad EAS exome AF: 0.169

Gnomad SAS exome AF: 0.208

Gnomad FIN exome AF: 0.321

Gnomad NFE exome AF: 0.286

Gnomad OTH exome AF: 0.292

GnomAD4 exome AF: 0.271 AC: 393251 AN: 1452764 Hom.: 54232 Cov.: 35 AF XY: 0.269 AC XY: 194624 AN XY: 722372

Gnomad4 AFR exome AF: 0.237

Gnomad4 AMR exome AF: 0.308

Gnomad4 ASJ exome AF: 0.366

Gnomad4 EAS exome AF: 0.169

Gnomad4 SAS exome AF: 0.211

Gnomad4 FIN exome AF: 0.320

Gnomad4 NFE exome AF: 0.273

Gnomad4 OTH exome AF: 0.282

GnomAD4 genome AF: 0.271 AC: 41227 AN: 152112 Hom.: 5697 Cov.: 33 AF XY: 0.271 AC XY: 20179 AN XY: 74354

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.287

Alfa AF: 0.284 Hom.: 8149

Bravo AF: 0.272

Asia WGS AF: 0.186 AC: 647 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

PITRM1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	1.4
Dann	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs10175; hg19: chr10-3180298; COSMIC: COSV56525195; COSMIC: COSV56525195;