dbSNP rs3814593: PITRM1:c.1136+34C>A (chr10-3158880-G-T) – 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.1136+34C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,598,602 control chromosomes in the GnomAD database, including 59,262 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 0.28 ( 6085 hom., cov: 33)

Exomes 𝑓: 0.27 ( 53177 hom. )

Consequence

PITRM1
NM_014889.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0280

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014889.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PITRM1	NM_014889.4	MANE Select	c.1136+34C>A	intron	N/A	NP_055704.2
PITRM1	NM_001242307.2		c.1136+34C>A	intron	N/A	NP_001229236.1	Q5JRX3-2
PITRM1	NM_001347729.1		c.1112+34C>A	intron	N/A	NP_001334658.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PITRM1	ENST00000224949.9	TSL:1 MANE Select	c.1136+34C>A	intron	N/A	ENSP00000224949.4	Q5JRX3-1
PITRM1	ENST00000380989.6	TSL:1	c.1136+34C>A	intron	N/A	ENSP00000370377.2	Q5JRX3-2
PITRM1	ENST00000851395.1		c.1124+34C>A	intron	N/A	ENSP00000521454.1

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42727

AN:

152016

Hom.:

6088

Cov.:

show subpopulations

Gnomad AFR

AF:

0.295

Gnomad AMI

AF:

0.245

Gnomad AMR

AF:

0.283

Gnomad ASJ

AF:

0.229

Gnomad EAS

AF:

0.305

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.322

Gnomad MID

AF:

0.242

Gnomad NFE

AF:

0.266

Gnomad OTH

AF:

0.299

GnomAD2 exomes

AF:

0.288

AC:

70014

AN:

242940

AF XY:

0.287

show subpopulations

Gnomad AFR exome

AF:

0.300

Gnomad AMR exome

AF:

0.332

Gnomad ASJ exome

AF:

0.238

Gnomad EAS exome

AF:

0.303

Gnomad FIN exome

AF:

0.321

Gnomad NFE exome

AF:

0.269

Gnomad OTH exome

AF:

0.291

GnomAD4 exome

AF:

0.269

AC:

389432

AN:

1446468

Hom.:

53177

Cov.:

AF XY:

0.269

AC XY:

193527

AN XY:

719680

show subpopulations

African (AFR)

AF:

0.304

AC:

9963

AN:

32786

American (AMR)

AF:

0.328

AC:

14063

AN:

42864

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

6055

AN:

25710

East Asian (EAS)

AF:

0.309

AC:

12233

AN:

39586

South Asian (SAS)

AF:

0.285

AC:

24129

AN:

84668

European-Finnish (FIN)

AF:

0.315

AC:

16764

AN:

53184

Middle Eastern (MID)

AF:

0.274

AC:

1558

AN:

5684

European-Non Finnish (NFE)

AF:

0.262

AC:

288481

AN:

1102258

Other (OTH)

AF:

0.271

AC:

16186

AN:

59728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

11790

23579

35369

47158

58948

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9766

19532

29298

39064

48830

<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:

0.281

AC:

42747

AN:

152134

Hom.:

6085

Cov.:

AF XY:

0.283

AC XY:

21031

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.295

AC:

12238

AN:

41492

American (AMR)

AF:

0.282

AC:

4317

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

795

AN:

3466

East Asian (EAS)

AF:

0.304

AC:

1574

AN:

5176

South Asian (SAS)

AF:

0.295

AC:

1422

AN:

4822

European-Finnish (FIN)

AF:

0.322

AC:

3408

AN:

10588

Middle Eastern (MID)

AF:

0.243

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.266

AC:

18067

AN:

67992

Other (OTH)

AF:

0.300

AC:

632

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1606

3212

4817

6423

8029

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

448

896

1344

1792

2240

<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:

0.271

Hom.:

4094

Bravo

AF:

0.283

Asia WGS

AF:

0.284

AC:

988

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.6

(source)

DANN

Benign

0.52

PhyloP100

0.028

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over