rs768575153

Variant names:

• chr10-3138075-C-A
• rs768575153
• NM_014889.4:c.3070G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-3138075-C-A
• chr10-3138075-C-G
• chr10-3138075-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_014889.4(PITRM1):​c.3070G>T​(p.Glu1024*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000137 in 1,458,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PITRM1 NM_014889.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.77
• Publications: 0 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: Illumina, Labcorp Genetics (formerly Invitae)

ENSG00000278419 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0141 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

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.3070G>T	p.Glu1024*	stop_gained	Exon 27 of 27	NP_055704.2
	PITRM1	NM_001242307.2		c.3073G>T	p.Glu1025*	stop_gained	Exon 27 of 27	NP_001229236.1	Q5JRX3-2
	PITRM1	NM_001347729.1		c.3046G>T	p.Glu1016*	stop_gained	Exon 27 of 27	NP_001334658.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PITRM1	ENST00000224949.9	TSL:1 MANE Select	c.3070G>T	p.Glu1024*	stop_gained	Exon 27 of 27	ENSP00000224949.4	Q5JRX3-1
	PITRM1	ENST00000380989.6	TSL:1	c.3073G>T	p.Glu1025*	stop_gained	Exon 27 of 27	ENSP00000370377.2	Q5JRX3-2
	PITRM1	ENST00000464395.1	TSL:1	n.2893G>T		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458144 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 724802

African (AFR) AF: 0.00 AC: 0 AN: 33414

American (AMR) AF: 0.00 AC: 0 AN: 44320

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25964

East Asian (EAS) AF: 0.00 AC: 0 AN: 39600

South Asian (SAS) AF: 0.00 AC: 0 AN: 85098

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110592

Other (OTH) AF: 0.00 AC: 0 AN: 60264

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.52	D
BayesDel_noAF	Pathogenic	0.51
CADD	Pathogenic	49
DANN	Uncertain	0.99
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.95	D
PhyloP100		4.8
Vest4		0.22
GERP RS		5.8
Mutation Taster		=3/197	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs768575153; hg19: chr10-3180267;