14-35212966-T-C

Variant names:

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

Variant summary

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

The NM_014672.4(PRORP):​c.1275+32189T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,234 control chromosomes in the GnomAD database, including 3,548 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 0.19 (3548 hom., 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

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>C		intron	N/A	NP_055487.2
	PRORP	NM_001414503.1		c.1275+32189T>C		intron	N/A	NP_001401432.1	O15091-1
	PRORP	NM_001256678.2		c.1227+32189T>C		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>C		intron	N/A	ENSP00000440915.2	O15091-1
	PRORP	ENST00000605870.5	TSL:1	c.159+32189T>C		intron	N/A	ENSP00000474299.1	O15091-3
	ENSG00000258790	ENST00000557565.1	TSL:2	n.1275+32189T>C		intron	N/A	ENSP00000454657.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29212 AN: 152116 Hom.: 3549 Cov.: 32

Gnomad AFR AF: 0.0518

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.192 AC: 29215 AN: 152234 Hom.: 3548 Cov.: 32 AF XY: 0.199 AC XY: 14779 AN XY: 74422

African (AFR) AF: 0.0520 AC: 2161 AN: 41574

American (AMR) AF: 0.154 AC: 2357 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 527 AN: 3472

East Asian (EAS) AF: 0.329 AC: 1701 AN: 5174

South Asian (SAS) AF: 0.196 AC: 946 AN: 4824

European-Finnish (FIN) AF: 0.359 AC: 3797 AN: 10578

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17244 AN: 68006

Other (OTH) AF: 0.184 AC: 387 AN: 2108

Alfa AF: 0.233 Hom.: 12671

Bravo AF: 0.170

Asia WGS AF: 0.246 AC: 855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.9
DANN	Benign	0.51
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;