chr14-35225975-T-A

Variant names:

• chr14-35225975-T-A
• rs8008319
• NM_014672.4:c.1276-40752T>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.1276-40752T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 152,186 control chromosomes in the GnomAD database, including 50,488 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 0.81 (50488 hom., cov: 32)
• Consequence: PRORP NM_014672.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 3 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=-0.57).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRORP	NM_014672.4	c.1276-40752T>A		intron_variant	Intron 5 of 7	ENST00000534898.9	NP_055487.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRORP	ENST00000534898.9	c.1276-40752T>A		intron_variant	Intron 5 of 7	1	NM_014672.4	ENSP00000440915.2
ENSG00000258790	ENST00000557565.1	n.1276-40752T>A		intron_variant	Intron 5 of 14	2		ENSP00000454657.1

Frequencies

GnomAD3 genomes AF: 0.814 AC: 123800 AN: 152068 Hom.: 50440 Cov.: 32

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.846

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.822

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

GnomAD4 genome AF: 0.814 AC: 123910 AN: 152186 Hom.: 50488 Cov.: 32 AF XY: 0.813 AC XY: 60490 AN XY: 74398

African (AFR) AF: 0.845 AC: 35102 AN: 41544

American (AMR) AF: 0.847 AC: 12942 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.802 AC: 2786 AN: 3472

East Asian (EAS) AF: 0.802 AC: 4147 AN: 5174

South Asian (SAS) AF: 0.773 AC: 3720 AN: 4812

European-Finnish (FIN) AF: 0.751 AC: 7943 AN: 10572

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.804 AC: 54659 AN: 68008

Other (OTH) AF: 0.823 AC: 1739 AN: 2114

Alfa AF: 0.798 Hom.: 6035

Bravo AF: 0.823

Asia WGS AF: 0.786 AC: 2735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.2
DANN	Benign	0.84
PhyloP100		1.3

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: rs8008319; hg19: chr14-35695181;