rs12586317

Variant names:

• chr14-35212966-T-A
• rs12586317
• NM_014672.4:c.1275+32189T>A

Your query was ambiguous. Multiple possible variants found:

• chr14-35212966-T-A
• chr14-35212966-T-C
• chr14-35212966-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014672.4(PRORP):​c.1275+32189T>A variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRORP NM_014672.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• Publications: 31 publications found

Genes affected

PRORP (HGNC:19958): (protein only RNase P catalytic subunit) Enables ribonuclease P activity. Involved in mitochondrial tRNA 5'-end processing. Located in mitochondrion and nucleoplasm. Part of mitochondrial ribonuclease P complex. [provided by Alliance of Genome Resources, Apr 2022]

PRORP Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• combined oxidative phosphorylation deficiency 54

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ENSG00000258790 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014672.4. 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
	PRORP	NM_014672.4	MANE Select	c.1275+32189T>A		intron	N/A	NP_055487.2
	PRORP	NM_001414503.1		c.1275+32189T>A		intron	N/A	NP_001401432.1	O15091-1
	PRORP	NM_001256678.2		c.1227+32189T>A		intron	N/A	NP_001243607.1	O15091-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRORP	ENST00000534898.9	TSL:1 MANE Select	c.1275+32189T>A		intron	N/A	ENSP00000440915.2	O15091-1
	PRORP	ENST00000605870.5	TSL:1	c.159+32189T>A		intron	N/A	ENSP00000474299.1	O15091-3
	ENSG00000258790	ENST00000557565.1	TSL:2	n.1275+32189T>A		intron	N/A	ENSP00000454657.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.4
DANN	Benign	0.65
PhyloP100		0.21
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

dbSNP: rs12586317; hg19: chr14-35682172;