rs12436663

Variant names:

• chr14-35169914-G-A
• rs12436663
• NM_014672.4:c.1168-10756G>A

Variant summary

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

The NM_014672.4(PRORP):​c.1168-10756G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,186 control chromosomes in the GnomAD database, including 2,820 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 0.18 (2820 hom., cov: 32)
• Consequence: PRORP NM_014672.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.335
• Publications: 10 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):

• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRORP	NM_014672.4	c.1168-10756G>A		intron_variant	Intron 4 of 7	ENST00000534898.9	NP_055487.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRORP	ENST00000534898.9	c.1168-10756G>A		intron_variant	Intron 4 of 7	1	NM_014672.4	ENSP00000440915.2
ENSG00000258790	ENST00000557565.1	n.1168-10756G>A		intron_variant	Intron 4 of 14	2		ENSP00000454657.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27926 AN: 152068 Hom.: 2822 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.184 AC: 27942 AN: 152186 Hom.: 2820 Cov.: 32 AF XY: 0.183 AC XY: 13626 AN XY: 74380

African (AFR) AF: 0.236 AC: 9800 AN: 41512

American (AMR) AF: 0.267 AC: 4078 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 495 AN: 3470

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5186

South Asian (SAS) AF: 0.179 AC: 861 AN: 4818

European-Finnish (FIN) AF: 0.127 AC: 1348 AN: 10602

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10736 AN: 68008

Other (OTH) AF: 0.165 AC: 349 AN: 2112

Alfa AF: 0.175 Hom.: 5922

Bravo AF: 0.197

Asia WGS AF: 0.0830 AC: 291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.64
PhyloP100		0.34

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: rs12436663; hg19: chr14-35639120;