dbSNP rs781167579: PITRM1:p.Pro823Ser (chr10-3144357-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014889.4(PITRM1):c.2467C>T(p.Pro823Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000148 in 1,552,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

PITRM1
NM_014889.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.865

Publications

1 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:

ENSG00000278419 (HGNC:):

ENSG00000278419 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08119345).

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	HGVSp	Effect	Exon Rank	Protein	UniProt
PITRM1	NM_014889.4	MANE Select	c.2467C>T	p.Pro823Ser	missense	Exon 22 of 27	NP_055704.2
PITRM1	NM_001242307.2		c.2470C>T	p.Pro824Ser	missense	Exon 22 of 27	NP_001229236.1	Q5JRX3-2
PITRM1	NM_001347729.1		c.2443C>T	p.Pro815Ser	missense	Exon 22 of 27	NP_001334658.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PITRM1	ENST00000224949.9	TSL:1 MANE Select	c.2467C>T	p.Pro823Ser	missense	Exon 22 of 27	ENSP00000224949.4	Q5JRX3-1
PITRM1	ENST00000380989.6	TSL:1	c.2470C>T	p.Pro824Ser	missense	Exon 22 of 27	ENSP00000370377.2	Q5JRX3-2
PITRM1	ENST00000464395.1	TSL:1	n.2060C>T		non_coding_transcript_exon	Exon 4 of 9

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000122

AC:

AN:

164270

AF XY:

0.0000115

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000305

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000136

AC:

AN:

1400838

Hom.:

Cov.:

AF XY:

0.0000101

AC XY:

AN XY:

691838

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31678

American (AMR)

AF:

0.00

AC:

AN:

36354

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25176

East Asian (EAS)

AF:

0.00

AC:

AN:

36540

South Asian (SAS)

AF:

0.00

AC:

AN:

79158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49762

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.0000158

AC:

AN:

1078438

Other (OTH)

AF:

0.0000345

AC:

AN:

58048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000263

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41418

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5204

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.00000880

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.029

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.093

LIST_S2

Benign

0.55

M_CAP

Benign

0.019

MetaRNN

Benign

0.081

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

0.86

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.6

REVEL

Benign

0.068

Sift

Benign

0.097

Sift4G

Benign

0.38

Polyphen

0.0030

Vest4

0.15

MVP

0.31

MPC

0.052

ClinPred

0.037

GERP RS

2.9

PromoterAI

0.016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.053

gMVP

0.38

Mutation Taster

=75/25

polymorphism

(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

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