rs2279216

Positions:

• chr10-3138759-G-A
• chr10-3138759-G-T

Variant summary

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

The NM_014889.4(PITRM1):​c.2917+145C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 831,298 control chromosomes in the GnomAD database, including 27,138 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 0.20 (3898 hom., cov: 34)
  • Exomes 𝑓: 0.25 (23240 hom.)
• Consequence: PITRM1 NM_014889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.642

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PITRM1	NM_014889.4	c.2917+145C>T		intron_variant		ENST00000224949.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PITRM1	ENST00000224949.9	c.2917+145C>T		intron_variant		1	NM_014889.4	P3

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31106 AN: 152026 Hom.: 3897 Cov.: 34

Gnomad AFR AF: 0.0548

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.213

GnomAD4 exome AF: 0.254 AC: 172754 AN: 679154 Hom.: 23240 Cov.: 8 AF XY: 0.255 AC XY: 93471 AN XY: 366628

Gnomad4 AFR exome AF: 0.0516

Gnomad4 AMR exome AF: 0.155

Gnomad4 ASJ exome AF: 0.239

Gnomad4 EAS exome AF: 0.214

Gnomad4 SAS exome AF: 0.244

Gnomad4 FIN exome AF: 0.226

Gnomad4 NFE exome AF: 0.286

Gnomad4 OTH exome AF: 0.245

GnomAD4 genome AF: 0.204 AC: 31107 AN: 152144 Hom.: 3898 Cov.: 34 AF XY: 0.203 AC XY: 15124 AN XY: 74388

Gnomad4 AFR AF: 0.0547

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.210

Alfa AF: 0.264 Hom.: 11392

Bravo AF: 0.195

Asia WGS AF: 0.204 AC: 712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.5
DANN	Benign	0.70

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: rs2279216; hg19: chr10-3180951; COSMIC: COSV56529716; COSMIC: COSV56529716;