rs7157492

Variant names:

• chr14-35258383-G-A
• rs7157492
• NM_014672.4:c.1276-8344G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-35258383-G-A
• chr14-35258383-G-T

Variant summary

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

The NM_014672.4(PRORP):​c.1276-8344G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 152,002 control chromosomes in the GnomAD database, including 45,323 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 0.77 (45323 hom., cov: 32)
• Consequence: PRORP NM_014672.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRORP	NM_014672.4	c.1276-8344G>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.1276-8344G>A		intron_variant	Intron 5 of 7	1	NM_014672.4	ENSP00000440915.2
ENSG00000258790	ENST00000557565.1	n.1276-8344G>A		intron_variant	Intron 5 of 14	2		ENSP00000454657.1

Frequencies

GnomAD3 genomes AF: 0.772 AC: 117195 AN: 151884 Hom.: 45277 Cov.: 32

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.777

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

GnomAD4 genome AF: 0.772 AC: 117303 AN: 152002 Hom.: 45323 Cov.: 32 AF XY: 0.772 AC XY: 57377 AN XY: 74294

African (AFR) AF: 0.815 AC: 33773 AN: 41446

American (AMR) AF: 0.810 AC: 12377 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2749 AN: 3468

East Asian (EAS) AF: 0.802 AC: 4152 AN: 5178

South Asian (SAS) AF: 0.754 AC: 3634 AN: 4818

European-Finnish (FIN) AF: 0.716 AC: 7534 AN: 10520

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.745 AC: 50650 AN: 67980

Other (OTH) AF: 0.775 AC: 1639 AN: 2114

Alfa AF: 0.660 Hom.: 1826

Bravo AF: 0.781

Asia WGS AF: 0.781 AC: 2715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.9
DANN	Benign	0.28
PhyloP100		0.36

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: rs7157492; hg19: chr14-35727589;