NM_014672.4:c.1275+32189T>C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000258790 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRORP	NM_014672.4	c.1275+32189T>C		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.1275+32189T>C		intron_variant	Intron 5 of 7	1	NM_014672.4	ENSP00000440915.2
ENSG00000258790	ENST00000557565.1	n.1275+32189T>C		intron_variant	Intron 5 of 14	2		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

Gnomad4 AFR AF: 0.0520

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.184

Alfa AF: 0.242 Hom.: 5316

Bravo AF: 0.170

Asia WGS AF: 0.246 AC: 855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs12586317; hg19: chr14-35682172;