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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITRM1	NM_014889.4 link	c.1136+34C>A		intron_variant	Intron 10 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.1136+34C>A		intron_variant	Intron 10 of 26	1	NM_014889.4	ENSP00000224949.4		Q5JRX3-1

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 v4.3

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

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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