dbSNP rs1127047: PITRM1:p.Thr109Thr (chr10-3166320-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014889.4(PITRM1):c.327C>T(p.Thr109Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0396 in 1,608,096 control chromosomes in the GnomAD database, including 1,512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 239 hom., cov: 33)

Exomes 𝑓: 0.039 ( 1273 hom. )

Consequence

PITRM1
NM_014889.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.55

Publications

11 publications found

Variant links:

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]

PITRM1 links:

PITRM1-AS1 (HGNC:44675): (PITRM1 antisense RNA 1)

PITRM1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 10-3166320-G-A is Benign according to our data. Variant chr10-3166320-G-A is described in ClinVar as Benign. ClinVar VariationId is 1546017.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.55 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITRM1	NM_014889.4 link	c.327C>T	p.Thr109Thr	synonymous_variant	Exon 4 of 27	ENST00000224949.9	NP_055704.2	Q5JRX3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITRM1	ENST00000224949.9 link	c.327C>T	p.Thr109Thr	synonymous_variant	Exon 4 of 27	1	NM_014889.4	ENSP00000224949.4		Q5JRX3-1

Frequencies

GnomAD3 genomes

AF:

0.0498

AC:

7441

AN:

149566

Hom.:

241

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0740

Gnomad AMI

AF:

0.0525

Gnomad AMR

AF:

0.0666

Gnomad ASJ

AF:

0.0316

Gnomad EAS

AF:

0.0232

Gnomad SAS

AF:

0.0424

Gnomad FIN

AF:

0.0421

Gnomad MID

AF:

0.0584

Gnomad NFE

AF:

0.0356

Gnomad OTH

AF:

0.0584

GnomAD2 exomes

AF:

0.0469

AC:

11549

AN:

246376

AF XY:

0.0446

show subpopulations

Gnomad AFR exome

AF:

0.0740

Gnomad AMR exome

AF:

0.0912

Gnomad ASJ exome

AF:

0.0355

Gnomad EAS exome

AF:

0.0232

Gnomad FIN exome

AF:

0.0418

Gnomad NFE exome

AF:

0.0354

Gnomad OTH exome

AF:

0.0410

GnomAD4 exome

AF:

0.0386

AC:

56266

AN:

1458406

Hom.:

1273

Cov.:

AF XY:

0.0384

AC XY:

27876

AN XY:

725612

show subpopulations

African (AFR)

AF:

0.0775

AC:

2585

AN:

33342

American (AMR)

AF:

0.0865

AC:

3854

AN:

44580

Ashkenazi Jewish (ASJ)

AF:

0.0342

AC:

892

AN:

26100

East Asian (EAS)

AF:

0.0217

AC:

858

AN:

39620

South Asian (SAS)

AF:

0.0481

AC:

4141

AN:

86042

European-Finnish (FIN)

AF:

0.0413

AC:

2201

AN:

53264

Middle Eastern (MID)

AF:

0.0436

AC:

250

AN:

5732

European-Non Finnish (NFE)

AF:

0.0351

AC:

38944

AN:

1109464

Other (OTH)

AF:

0.0422

AC:

2541

AN:

60262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

2504

5008

7513

10017

12521

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1500

3000

4500

6000

7500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0498

AC:

7453

AN:

149690

Hom.:

239

Cov.:

AF XY:

0.0502

AC XY:

3663

AN XY:

73034

show subpopulations

African (AFR)

AF:

0.0740

AC:

3011

AN:

40714

American (AMR)

AF:

0.0668

AC:

1004

AN:

15026

Ashkenazi Jewish (ASJ)

AF:

0.0316

AC:

109

AN:

3448

East Asian (EAS)

AF:

0.0233

AC:

118

AN:

5068

South Asian (SAS)

AF:

0.0425

AC:

199

AN:

4684

European-Finnish (FIN)

AF:

0.0421

AC:

434

AN:

10320

Middle Eastern (MID)

AF:

0.0625

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0356

AC:

2392

AN:

67202

Other (OTH)

AF:

0.0592

AC:

121

AN:

2044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

369

738

1106

1475

1844

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0432

Hom.:

244

Bravo

AF:

0.0539

Asia WGS

AF:

0.0410

AC:

142

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

PITRM1-related disorder

Benign:1

Nov 04, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.066

(source)

DANN

Benign

0.80

PhyloP100

-4.6

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over