chr10-3138759-G-A

Variant names:

• chr10-3138759-G-A
• rs2279216
• NM_014889.4:c.2917+145C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia, autosomal recessive 30

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Illumina

ENSG00000278419 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.2917+145C>T		intron	N/A	NP_055704.2
	PITRM1	NM_001242307.2		c.2920+145C>T		intron	N/A	NP_001229236.1
	PITRM1	NM_001347729.1		c.2893+145C>T		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.2917+145C>T		intron	N/A	ENSP00000224949.4
	PITRM1	ENST00000380989.6	TSL:1	c.2920+145C>T		intron	N/A	ENSP00000370377.2
	PITRM1	ENST00000464395.1	TSL:1	n.2740+145C>T		intron	N/A

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

African (AFR) AF: 0.0516 AC: 956 AN: 18518

American (AMR) AF: 0.155 AC: 6695 AN: 43332

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 5053 AN: 21164

East Asian (EAS) AF: 0.214 AC: 7738 AN: 36240

South Asian (SAS) AF: 0.244 AC: 17018 AN: 69860

European-Finnish (FIN) AF: 0.226 AC: 11907 AN: 52720

Middle Eastern (MID) AF: 0.175 AC: 742 AN: 4230

European-Non Finnish (NFE) AF: 0.286 AC: 114117 AN: 398326

Other (OTH) AF: 0.245 AC: 8528 AN: 34764

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

African (AFR) AF: 0.0547 AC: 2272 AN: 41548

American (AMR) AF: 0.204 AC: 3117 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 836 AN: 3470

East Asian (EAS) AF: 0.222 AC: 1145 AN: 5158

South Asian (SAS) AF: 0.240 AC: 1156 AN: 4822

European-Finnish (FIN) AF: 0.219 AC: 2318 AN: 10584

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19484 AN: 67968

Other (OTH) AF: 0.210 AC: 444 AN: 2116

Alfa AF: 0.252 Hom.: 16778

Bravo AF: 0.195

Asia WGS AF: 0.204 AC: 712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.5
DANN	Benign	0.70
PhyloP100		0.64
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: rs2279216; hg19: chr10-3180951; COSMIC: COSV56529716; COSMIC: COSV56529716;