chr10-3138264-G-A

Variant names:

• chr10-3138264-G-A
• NM_014889.4:c.2991C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_014889.4(PITRM1):​c.2991C>T​(p.Ser997Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PITRM1 NM_014889.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.830
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-3138264-G-A is Benign according to our data. Variant chr10-3138264-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1992536.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.83 with no splicing effect.

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.2991C>T	p.Ser997Ser	synonymous	Exon 26 of 27	NP_055704.2
	PITRM1	NM_001242307.2		c.2994C>T	p.Ser998Ser	synonymous	Exon 26 of 27	NP_001229236.1	Q5JRX3-2
	PITRM1	NM_001347729.1		c.2967C>T	p.Ser989Ser	synonymous	Exon 26 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.2991C>T	p.Ser997Ser	synonymous	Exon 26 of 27	ENSP00000224949.4	Q5JRX3-1
	PITRM1	ENST00000380989.6	TSL:1	c.2994C>T	p.Ser998Ser	synonymous	Exon 26 of 27	ENSP00000370377.2	Q5JRX3-2
	PITRM1	ENST00000464395.1	TSL:1	n.2814C>T		non_coding_transcript_exon	Exon 8 of 9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.6
DANN	Benign	0.74
PhyloP100		0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

hg19: chr10-3180456;