rs4242746

Variant names:

• chr10-3159873-T-C
• rs4242746
• NM_014889.4:c.982A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-3159873-T-C
• chr10-3159873-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014889.4(PITRM1):​c.982A>G​(p.Ile328Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 1,597,334 control chromosomes in the GnomAD database, including 367,165 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (32026 hom., cov: 32)
  • Exomes 𝑓: 0.68 (335139 hom.)
• Consequence: PITRM1 NM_014889.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.299
• Publications: 43 publications found

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-AS1 (HGNC:44675): (PITRM1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.5671096E-6).
• BP6: Variant 10-3159873-T-C is Benign according to our data. Variant chr10-3159873-T-C is described in ClinVar as Benign. ClinVar VariationId is 1607453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.675 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PITRM1	NM_014889.4	MANE Select	c.982A>G	p.Ile328Val	missense	Exon 9 of 27	NP_055704.2
	PITRM1	NM_001242307.2		c.982A>G	p.Ile328Val	missense	Exon 9 of 27	NP_001229236.1	Q5JRX3-2
	PITRM1	NM_001347729.1		c.958A>G	p.Ile320Val	missense	Exon 9 of 27	NP_001334658.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PITRM1	ENST00000224949.9	TSL:1 MANE Select	c.982A>G	p.Ile328Val	missense	Exon 9 of 27	ENSP00000224949.4	Q5JRX3-1
	PITRM1	ENST00000380989.6	TSL:1	c.982A>G	p.Ile328Val	missense	Exon 9 of 27	ENSP00000370377.2	Q5JRX3-2
	PITRM1	ENST00000851395.1		c.970A>G	p.Ile324Val	missense	Exon 9 of 27	ENSP00000521454.1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98393 AN: 151918 Hom.: 32011 Cov.: 32

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.647

GnomAD2 exomes AF: 0.638 AC: 150572 AN: 235956 AF XY: 0.643

Gnomad AFR exome AF: 0.627

Gnomad AMR exome AF: 0.534

Gnomad ASJ exome AF: 0.561

Gnomad EAS exome AF: 0.580

Gnomad FIN exome AF: 0.678

Gnomad NFE exome AF: 0.672

Gnomad OTH exome AF: 0.638

GnomAD4 exome AF: 0.679 AC: 981669 AN: 1445296 Hom.: 335139 Cov.: 30 AF XY: 0.678 AC XY: 487073 AN XY: 718210

African (AFR) AF: 0.634 AC: 21061 AN: 33236

American (AMR) AF: 0.537 AC: 23361 AN: 43540

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 14656 AN: 25886

East Asian (EAS) AF: 0.592 AC: 23383 AN: 39468

South Asian (SAS) AF: 0.668 AC: 56089 AN: 84018

European-Finnish (FIN) AF: 0.679 AC: 35897 AN: 52896

Middle Eastern (MID) AF: 0.557 AC: 3199 AN: 5748

European-Non Finnish (NFE) AF: 0.695 AC: 764805 AN: 1100668

Other (OTH) AF: 0.655 AC: 39218 AN: 59836

GnomAD4 genome AF: 0.648 AC: 98450 AN: 152038 Hom.: 32026 Cov.: 32 AF XY: 0.644 AC XY: 47882 AN XY: 74304

African (AFR) AF: 0.628 AC: 26046 AN: 41442

American (AMR) AF: 0.570 AC: 8708 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1957 AN: 3470

East Asian (EAS) AF: 0.589 AC: 3037 AN: 5154

South Asian (SAS) AF: 0.666 AC: 3208 AN: 4818

European-Finnish (FIN) AF: 0.676 AC: 7141 AN: 10560

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.681 AC: 46277 AN: 67992

Other (OTH) AF: 0.643 AC: 1357 AN: 2110

Alfa AF: 0.664 Hom.: 159872

Bravo AF: 0.637

TwinsUK AF: 0.698 AC: 2588

ALSPAC AF: 0.711 AC: 2739

ESP6500AA AF: 0.680 AC: 1373

ESP6500EA AF: 0.691 AC: 2964

ExAC AF: 0.630 AC: 75967

Asia WGS AF: 0.599 AC: 2085 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.34
DANN	Benign	0.52
DEOGEN2	Benign	0.0069	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.0000076	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.57	N
PhyloP100		0.30
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.032
Sift	Benign	1.0	T
Sift4G	Benign	0.73	T
Vest4		0.057
MPC		0.045
ClinPred		0.0019	T
GERP RS		0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.026
gMVP		0.24
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4242746; hg19: chr10-3202065; COSMIC: COSV56527479; COSMIC: COSV56527479;