rs3814593

Positions:

• chr10-3158880-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.1136+34C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,598,602 control chromosomes in the GnomAD database, including 59,262 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 0.28 (6085 hom., cov: 33)
  • Exomes 𝑓: 0.27 (53177 hom.)
• Consequence: PITRM1 NM_014889.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PITRM1	NM_014889.4	c.1136+34C>A		intron_variant		ENST00000224949.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PITRM1	ENST00000224949.9	c.1136+34C>A		intron_variant		1	NM_014889.4	P3
PITRM1-AS1	ENST00000598280.5	n.270-5215G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42727 AN: 152016 Hom.: 6088 Cov.: 33

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.299

GnomAD3 exomes AF: 0.288 AC: 70014 AN: 242940 Hom.: 10305 AF XY: 0.287 AC XY: 37821 AN XY: 131782

Gnomad AFR exome AF: 0.300

Gnomad AMR exome AF: 0.332

Gnomad ASJ exome AF: 0.238

Gnomad EAS exome AF: 0.303

Gnomad SAS exome AF: 0.290

Gnomad FIN exome AF: 0.321

Gnomad NFE exome AF: 0.269

Gnomad OTH exome AF: 0.291

GnomAD4 exome AF: 0.269 AC: 389432 AN: 1446468 Hom.: 53177 Cov.: 28 AF XY: 0.269 AC XY: 193527 AN XY: 719680

Gnomad4 AFR exome AF: 0.304

Gnomad4 AMR exome AF: 0.328

Gnomad4 ASJ exome AF: 0.236

Gnomad4 EAS exome AF: 0.309

Gnomad4 SAS exome AF: 0.285

Gnomad4 FIN exome AF: 0.315

Gnomad4 NFE exome AF: 0.262

Gnomad4 OTH exome AF: 0.271

GnomAD4 genome AF: 0.281 AC: 42747 AN: 152134 Hom.: 6085 Cov.: 33 AF XY: 0.283 AC XY: 21031 AN XY: 74354

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.300

Alfa AF: 0.269 Hom.: 2972

Bravo AF: 0.283

Asia WGS AF: 0.284 AC: 988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.52

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: rs3814593; hg19: chr10-3201072; COSMIC: COSV56528111; COSMIC: COSV56528111;