chr10-3138096-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014889.4(PITRM1):c.3049G>A(p.Gly1017Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0262 in 1,609,880 control chromosomes in the GnomAD database, including 672 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 40 hom., cov: 34)

Exomes 𝑓: 0.027 ( 632 hom. )

Consequence

PITRM1
NM_014889.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.84

Publications

14 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 Gene-Disease associations (from GenCC):

spinocerebellar ataxia, autosomal recessive 30
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Illumina

PITRM1 links:

ENSG00000278419 (HGNC:):

ENSG00000278419 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0100236535).

BP6

Variant 10-3138096-C-T is Benign according to our data. Variant chr10-3138096-C-T is described in ClinVar as [Benign]. Clinvar id is 1628450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0188 (2866/152290) while in subpopulation NFE AF = 0.0307 (2089/68030). AF 95% confidence interval is 0.0296. There are 40 homozygotes in GnomAd4. There are 1258 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 40 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITRM1	NM_014889.4 link	c.3049G>A	p.Gly1017Ser	missense_variant	Exon 27 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.3049G>A	p.Gly1017Ser	missense_variant	Exon 27 of 27	1	NM_014889.4	ENSP00000224949.4		Q5JRX3-1

Frequencies

GnomAD3 genomes

AF:

0.0188

AC:

2867

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00586

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0186

Gnomad ASJ

AF:

0.0133

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.0118

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0307

Gnomad OTH

AF:

0.0258

GnomAD2 exomes

AF:

0.0180

AC:

4374

AN:

242422

AF XY:

0.0184

show subpopulations

Gnomad AFR exome

AF:

0.00446

Gnomad AMR exome

AF:

0.0122

Gnomad ASJ exome

AF:

0.0108

Gnomad EAS exome

AF:

0.000226

Gnomad FIN exome

AF:

0.0110

Gnomad NFE exome

AF:

0.0304

Gnomad OTH exome

AF:

0.0212

GnomAD4 exome

AF:

0.0270

AC:

39326

AN:

1457590

Hom.:

632

Cov.:

AF XY:

0.0264

AC XY:

19128

AN XY:

724570

show subpopulations

African (AFR)

AF:

0.00488

AC:

163

AN:

33416

American (AMR)

AF:

0.0139

AC:

615

AN:

44314

Ashkenazi Jewish (ASJ)

AF:

0.0117

AC:

303

AN:

25966

East Asian (EAS)

AF:

0.000126

AC:

AN:

39612

South Asian (SAS)

AF:

0.00249

AC:

212

AN:

85176

European-Finnish (FIN)

AF:

0.0127

AC:

676

AN:

53182

Middle Eastern (MID)

AF:

0.0165

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0323

AC:

35870

AN:

1109926

Other (OTH)

AF:

0.0230

AC:

1387

AN:

60232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

1665

3330

4994

6659

8324

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0188

AC:

2866

AN:

152290

Hom.:

Cov.:

AF XY:

0.0169

AC XY:

1258

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00585

AC:

243

AN:

41558

American (AMR)

AF:

0.0186

AC:

284

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0133

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.00166

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0118

AC:

125

AN:

10618

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0307

AC:

2089

AN:

68030

Other (OTH)

AF:

0.0251

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

147

294

442

589

736

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0265

Hom.:

131

Bravo

AF:

0.0191

TwinsUK

AF:

0.0353

AC:

131

ALSPAC

AF:

0.0309

AC:

119

ESP6500AA

AF:

0.00611

AC:

ESP6500EA

AF:

0.0314

AC:

266

ExAC

AF:

0.0176

AC:

2133

Asia WGS

AF:

0.00231

AC:

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

Feb 03, 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 19, 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

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;.;.;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.51

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.83

T;T;T;T

MetaRNN

Benign

0.010

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;.;.;.

PhyloP100

3.8

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.1

D;D;D;D

REVEL

Benign

0.20

Sift

Benign

0.051

T;T;T;T

Sift4G

Uncertain

0.056

T;T;T;T

Polyphen

0.99

D;.;.;.

Vest4

0.14

MPC

0.061

ClinPred

0.039

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.77

Mutation Taster

=76/24

polymorphism (auto)

(source)

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

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chr10-3138096-C-T

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