10-3138035-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014889.4(PITRM1):c.3110A>G(p.Gln1037Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 1,593,702 control chromosomes in the GnomAD database, including 404,664 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.70 (37522 hom., cov: 33)
  • Exomes 𝑓: 0.71 (367142 hom.)
• Consequence: PITRM1 NM_014889.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.939

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0319361E-6).
• BP6: Variant 10-3138035-T-C is Benign according to our data. Variant chr10-3138035-T-C is described in ClinVar as [Benign]. Clinvar id is 1598743.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PITRM1	NM_014889.4	c.3110A>G	p.Gln1037Arg	missense_variant	27/27	ENST00000224949.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PITRM1	ENST00000224949.9	c.3110A>G	p.Gln1037Arg	missense_variant	27/27	1	NM_014889.4	P3

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106666 AN: 151958 Hom.: 37495 Cov.: 33

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.712

GnomAD3 exomes AF: 0.702 AC: 163342 AN: 232586 Hom.: 57408 AF XY: 0.702 AC XY: 88250 AN XY: 125792

Gnomad AFR exome AF: 0.707

Gnomad AMR exome AF: 0.713

Gnomad ASJ exome AF: 0.612

Gnomad EAS exome AF: 0.738

Gnomad SAS exome AF: 0.716

Gnomad FIN exome AF: 0.688

Gnomad NFE exome AF: 0.701

Gnomad OTH exome AF: 0.687

GnomAD4 exome AF: 0.713 AC: 1027768 AN: 1441626 Hom.: 367142 Cov.: 29 AF XY: 0.712 AC XY: 510074 AN XY: 716474

Gnomad4 AFR exome AF: 0.713

Gnomad4 AMR exome AF: 0.707

Gnomad4 ASJ exome AF: 0.613

Gnomad4 EAS exome AF: 0.751

Gnomad4 SAS exome AF: 0.712

Gnomad4 FIN exome AF: 0.688

Gnomad4 NFE exome AF: 0.716

Gnomad4 OTH exome AF: 0.701

GnomAD4 genome AF: 0.702 AC: 106738 AN: 152076 Hom.: 37522 Cov.: 33 AF XY: 0.702 AC XY: 52191 AN XY: 74350

Gnomad4 AFR AF: 0.709

Gnomad4 AMR AF: 0.680

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.740

Gnomad4 SAS AF: 0.714

Gnomad4 FIN AF: 0.696

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.707

Alfa AF: 0.699 Hom.: 76750

Bravo AF: 0.703

TwinsUK AF: 0.717 AC: 2658

ALSPAC AF: 0.726 AC: 2799

ESP6500AA AF: 0.723 AC: 2947

ESP6500EA AF: 0.710 AC: 5936

ExAC AF: 0.688 AC: 82842

Asia WGS AF: 0.690 AC: 2399 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	2.8
Dann	Benign	0.39
DEOGEN2	Benign	0.019	T;.;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.38	T;T;T;T
MetaRNN	Benign	0.0000010	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-2.9	N;.;.;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.64	N;N;N;N
REVEL	Benign	0.11
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Vest4		0.028
MPC		0.054
ClinPred		0.0064	T
GERP RS		0.73
Varity_R		0.033
gMVP		0.41

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

LitVar

Other links and lift over

dbSNP: rs6901; hg19: chr10-3180227; COSMIC: COSV56528406; COSMIC: COSV56528406;