10-3148073-A-G

Position:

• chr10-3148073-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014889.4(PITRM1):​c.1993-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 1,612,778 control chromosomes in the GnomAD database, including 218,237 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 0.47 (17586 hom., cov: 33)
  • Exomes 𝑓: 0.52 (200651 hom.)
• Consequence: PITRM1 NM_014889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.731

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PITRM1	NM_014889.4	c.1993-10T>C		intron_variant		ENST00000224949.9	NP_055704.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PITRM1	ENST00000224949.9	c.1993-10T>C		intron_variant		1	NM_014889.4	ENSP00000224949.4

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72104 AN: 151910 Hom.: 17590 Cov.: 33

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.500

GnomAD3 exomes AF: 0.505 AC: 125915 AN: 249110 Hom.: 32278 AF XY: 0.510 AC XY: 68877 AN XY: 135138

Gnomad AFR exome AF: 0.365

Gnomad AMR exome AF: 0.482

Gnomad ASJ exome AF: 0.479

Gnomad EAS exome AF: 0.529

Gnomad SAS exome AF: 0.540

Gnomad FIN exome AF: 0.486

Gnomad NFE exome AF: 0.524

Gnomad OTH exome AF: 0.511

GnomAD4 exome AF: 0.523 AC: 763470 AN: 1460750 Hom.: 200651 Cov.: 36 AF XY: 0.523 AC XY: 379877 AN XY: 726758

Gnomad4 AFR exome AF: 0.370

Gnomad4 AMR exome AF: 0.479

Gnomad4 ASJ exome AF: 0.483

Gnomad4 EAS exome AF: 0.539

Gnomad4 SAS exome AF: 0.536

Gnomad4 FIN exome AF: 0.486

Gnomad4 NFE exome AF: 0.531

Gnomad4 OTH exome AF: 0.514

GnomAD4 genome AF: 0.474 AC: 72130 AN: 152028 Hom.: 17586 Cov.: 33 AF XY: 0.475 AC XY: 35283 AN XY: 74320

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.540

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.496

Alfa AF: 0.512 Hom.: 29031

Bravo AF: 0.472

Asia WGS AF: 0.504 AC: 1754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.10
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs4881111; hg19: chr10-3190265; COSMIC: COSV56533818; COSMIC: COSV56533818;