Genetic Variant NM_014889.4:c.2917+145C>T (chr10-3138759-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014889.4(PITRM1):c.2917+145C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 831,298 control chromosomes in the GnomAD database, including 27,138 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 0.20 ( 3898 hom., cov: 34)

Exomes 𝑓: 0.25 ( 23240 hom. )

Consequence

PITRM1
NM_014889.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.642

Publications

18 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 -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITRM1	NM_014889.4 link	c.2917+145C>T		intron_variant	Intron 25 of 26	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.2917+145C>T		intron_variant	Intron 25 of 26	1	NM_014889.4	ENSP00000224949.4		Q5JRX3-1

Frequencies

GnomAD3 genomes

AF:

0.205

AC:

31106

AN:

152026

Hom.:

3897

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0548

Gnomad AMI

AF:

0.322

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.221

Gnomad SAS

AF:

0.238

Gnomad FIN

AF:

0.219

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.287

Gnomad OTH

AF:

0.213

GnomAD4 exome

AF:

0.254

AC:

172754

AN:

679154

Hom.:

23240

Cov.:

AF XY:

0.255

AC XY:

93471

AN XY:

366628

show subpopulations

African (AFR)

AF:

0.0516

AC:

956

AN:

18518

American (AMR)

AF:

0.155

AC:

6695

AN:

43332

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

5053

AN:

21164

East Asian (EAS)

AF:

0.214

AC:

7738

AN:

36240

South Asian (SAS)

AF:

0.244

AC:

17018

AN:

69860

European-Finnish (FIN)

AF:

0.226

AC:

11907

AN:

52720

Middle Eastern (MID)

AF:

0.175

AC:

742

AN:

4230

European-Non Finnish (NFE)

AF:

0.286

AC:

114117

AN:

398326

Other (OTH)

AF:

0.245

AC:

8528

AN:

34764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

7245

14490

21735

28980

36225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1222

2444

3666

4888

6110

<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:

0.204

AC:

31107

AN:

152144

Hom.:

3898

Cov.:

AF XY:

0.203

AC XY:

15124

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0547

AC:

2272

AN:

41548

American (AMR)

AF:

0.204

AC:

3117

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

836

AN:

3470

East Asian (EAS)

AF:

0.222

AC:

1145

AN:

5158

South Asian (SAS)

AF:

0.240

AC:

1156

AN:

4822

European-Finnish (FIN)

AF:

0.219

AC:

2318

AN:

10584

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.287

AC:

19484

AN:

67968

Other (OTH)

AF:

0.210

AC:

444

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1217

2434

3650

4867

6084

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

338

676

1014

1352

1690

<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:

0.252

Hom.:

16778

Bravo

AF:

0.195

Asia WGS

AF:

0.204

AC:

712

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.5

(source)

DANN

Benign

0.70

PhyloP100

0.64

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over