10-3137983-C-T

Variant names:

• chr10-3137983-C-T
• rs12678
• ENST00000464395.1:n.2985G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000464395.1(PITRM1):​n.2985G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,054,544 control chromosomes in the GnomAD database, including 9,959 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 0.14 (1506 hom., cov: 33)
  • Exomes 𝑓: 0.13 (8453 hom.)
• Consequence: PITRM1 ENST00000464395.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505
• Publications: 14 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITRM1	NM_014889.4	c.*48G>A		3_prime_UTR_variant	Exon 27 of 27	ENST00000224949.9	NP_055704.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITRM1	ENST00000224949.9	c.*48G>A		3_prime_UTR_variant	Exon 27 of 27	1	NM_014889.4	ENSP00000224949.4

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21272 AN: 152046 Hom.: 1503 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.0898

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0495

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.137

GnomAD2 exomes AF: 0.125 AC: 20596 AN: 165316 AF XY: 0.126

Gnomad AFR exome AF: 0.162

Gnomad AMR exome AF: 0.0640

Gnomad ASJ exome AF: 0.104

Gnomad EAS exome AF: 0.0528

Gnomad FIN exome AF: 0.159

Gnomad NFE exome AF: 0.145

Gnomad OTH exome AF: 0.129

GnomAD4 exome AF: 0.132 AC: 119449 AN: 902380 Hom.: 8453 Cov.: 12 AF XY: 0.133 AC XY: 61776 AN XY: 464500

African (AFR) AF: 0.152 AC: 3352 AN: 22008

American (AMR) AF: 0.0677 AC: 2316 AN: 34192

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 2182 AN: 21364

East Asian (EAS) AF: 0.0559 AC: 1929 AN: 34480

South Asian (SAS) AF: 0.129 AC: 8835 AN: 68402

European-Finnish (FIN) AF: 0.157 AC: 7766 AN: 49436

Middle Eastern (MID) AF: 0.111 AC: 463 AN: 4174

European-Non Finnish (NFE) AF: 0.140 AC: 87429 AN: 626582

Other (OTH) AF: 0.124 AC: 5177 AN: 41742

GnomAD4 genome AF: 0.140 AC: 21282 AN: 152164 Hom.: 1506 Cov.: 33 AF XY: 0.139 AC XY: 10310 AN XY: 74374

African (AFR) AF: 0.162 AC: 6723 AN: 41510

American (AMR) AF: 0.0897 AC: 1372 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 387 AN: 3472

East Asian (EAS) AF: 0.0492 AC: 255 AN: 5182

South Asian (SAS) AF: 0.122 AC: 587 AN: 4822

European-Finnish (FIN) AF: 0.167 AC: 1768 AN: 10568

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9776 AN: 68000

Other (OTH) AF: 0.136 AC: 288 AN: 2112

Alfa AF: 0.123 Hom.: 967

Bravo AF: 0.132

Asia WGS AF: 0.0830 AC: 290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.3
DANN	Benign	0.71
PhyloP100		-0.51
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: rs12678; hg19: chr10-3180175; COSMIC: COSV56529699; COSMIC: COSV56529699;