NM_014889.4:c.1136+34C>A

Variant names:

• chr10-3158880-G-T
• rs3814593
• NM_014889.4:c.1136+34C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PITRM1	NM_014889.4	MANE Select	c.1136+34C>A		intron	N/A	NP_055704.2
	PITRM1	NM_001242307.2		c.1136+34C>A		intron	N/A	NP_001229236.1
	PITRM1	NM_001347729.1		c.1112+34C>A		intron	N/A	NP_001334658.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PITRM1	ENST00000224949.9	TSL:1 MANE Select	c.1136+34C>A		intron	N/A	ENSP00000224949.4
	PITRM1	ENST00000380989.6	TSL:1	c.1136+34C>A		intron	N/A	ENSP00000370377.2
	PITRM1	ENST00000678987.1		c.1088+34C>A		intron	N/A	ENSP00000504462.1

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

GnomAD2 exomes AF: 0.288 AC: 70014 AN: 242940 AF XY: 0.287

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 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

African (AFR) AF: 0.304 AC: 9963 AN: 32786

American (AMR) AF: 0.328 AC: 14063 AN: 42864

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 6055 AN: 25710

East Asian (EAS) AF: 0.309 AC: 12233 AN: 39586

South Asian (SAS) AF: 0.285 AC: 24129 AN: 84668

European-Finnish (FIN) AF: 0.315 AC: 16764 AN: 53184

Middle Eastern (MID) AF: 0.274 AC: 1558 AN: 5684

European-Non Finnish (NFE) AF: 0.262 AC: 288481 AN: 1102258

Other (OTH) AF: 0.271 AC: 16186 AN: 59728

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

African (AFR) AF: 0.295 AC: 12238 AN: 41492

American (AMR) AF: 0.282 AC: 4317 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 795 AN: 3466

East Asian (EAS) AF: 0.304 AC: 1574 AN: 5176

South Asian (SAS) AF: 0.295 AC: 1422 AN: 4822

European-Finnish (FIN) AF: 0.322 AC: 3408 AN: 10588

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.266 AC: 18067 AN: 67992

Other (OTH) AF: 0.300 AC: 632 AN: 2110

Alfa AF: 0.271 Hom.: 4094

Bravo AF: 0.283

Asia WGS AF: 0.284 AC: 988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.52
PhyloP100		0.028
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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