10-3138124-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_014889.4(PITRM1):c.3021A>G(p.Arg1007=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,598,882 control chromosomes in the GnomAD database, including 281,935 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (29132 hom., cov: 32)
  • Exomes 𝑓: 0.59 (252803 hom.)
• Consequence: PITRM1 NM_014889.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.00003535
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.360

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 10-3138124-T-C is Benign according to our data. Variant chr10-3138124-T-C is described in ClinVar as [Benign]. Clinvar id is 1600344.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.36 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PITRM1	NM_014889.4	c.3021A>G	p.Arg1007=	splice_region_variant, synonymous_variant	27/27	ENST00000224949.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PITRM1	ENST00000224949.9	c.3021A>G	p.Arg1007=	splice_region_variant, synonymous_variant	27/27	1	NM_014889.4	P3

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93831 AN: 151960 Hom.: 29106 Cov.: 32

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.612

GnomAD3 exomes AF: 0.592 AC: 141822 AN: 239608 Hom.: 42124 AF XY: 0.590 AC XY: 76572 AN XY: 129864

Gnomad AFR exome AF: 0.684

Gnomad AMR exome AF: 0.573

Gnomad ASJ exome AF: 0.561

Gnomad EAS exome AF: 0.515

Gnomad SAS exome AF: 0.538

Gnomad FIN exome AF: 0.678

Gnomad NFE exome AF: 0.598

Gnomad OTH exome AF: 0.603

GnomAD4 exome AF: 0.589 AC: 852281 AN: 1446804 Hom.: 252803 Cov.: 33 AF XY: 0.587 AC XY: 422561 AN XY: 719676

Gnomad4 AFR exome AF: 0.691

Gnomad4 AMR exome AF: 0.578

Gnomad4 ASJ exome AF: 0.554

Gnomad4 EAS exome AF: 0.527

Gnomad4 SAS exome AF: 0.537

Gnomad4 FIN exome AF: 0.671

Gnomad4 NFE exome AF: 0.590

Gnomad4 OTH exome AF: 0.586

GnomAD4 genome AF: 0.617 AC: 93903 AN: 152078 Hom.: 29132 Cov.: 32 AF XY: 0.616 AC XY: 45773 AN XY: 74334

Gnomad4 AFR AF: 0.683

Gnomad4 AMR AF: 0.580

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.672

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.610

Alfa AF: 0.593 Hom.: 45268

Bravo AF: 0.614

Asia WGS AF: 0.521 AC: 1813 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	6.5
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000035
dbscSNV1_RF	Benign	0.0020
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

Publications

LitVar

Other links and lift over

dbSNP: rs11414; hg19: chr10-3180316; COSMIC: COSV56527721; COSMIC: COSV56527721;