10-3148073-A-G

Variant names:

• chr10-3148073-A-G
• rs4881111
• NM_014889.4:c.1993-10T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 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 -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.

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.1993-10T>C		intron	N/A	NP_055704.2
	PITRM1	NM_001242307.2		c.1996-10T>C		intron	N/A	NP_001229236.1	Q5JRX3-2
	PITRM1	NM_001347729.1		c.1969-10T>C		intron	N/A	NP_001334658.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PITRM1	ENST00000224949.9	TSL:1 MANE Select	c.1993-10T>C		intron	N/A	ENSP00000224949.4	Q5JRX3-1
	PITRM1	ENST00000380989.6	TSL:1	c.1996-10T>C		intron	N/A	ENSP00000370377.2	Q5JRX3-2
	PITRM1-AS1	ENST00000430356.3	TSL:1	n.3449A>G		non_coding_transcript_exon	Exon 4 of 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

GnomAD2 exomes AF: 0.505 AC: 125915 AN: 249110 AF XY: 0.510

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 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

African (AFR) AF: 0.370 AC: 12373 AN: 33464

American (AMR) AF: 0.479 AC: 21428 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 12628 AN: 26132

East Asian (EAS) AF: 0.539 AC: 21397 AN: 39692

South Asian (SAS) AF: 0.536 AC: 46179 AN: 86234

European-Finnish (FIN) AF: 0.486 AC: 25932 AN: 53398

Middle Eastern (MID) AF: 0.478 AC: 2758 AN: 5764

European-Non Finnish (NFE) AF: 0.531 AC: 589739 AN: 1111010

Other (OTH) AF: 0.514 AC: 31036 AN: 60344

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

African (AFR) AF: 0.367 AC: 15230 AN: 41472

American (AMR) AF: 0.483 AC: 7375 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1650 AN: 3466

East Asian (EAS) AF: 0.540 AC: 2781 AN: 5148

South Asian (SAS) AF: 0.543 AC: 2621 AN: 4828

European-Finnish (FIN) AF: 0.482 AC: 5092 AN: 10570

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35700 AN: 67964

Other (OTH) AF: 0.496 AC: 1046 AN: 2108

Alfa AF: 0.506 Hom.: 65607

Bravo AF: 0.472

Asia WGS AF: 0.504 AC: 1754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.10
DANN	Benign	0.59
PhyloP100		0.73
PromoterAI		-0.0075	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4881111; hg19: chr10-3190265; COSMIC: COSV56533818; COSMIC: COSV56533818;