14-35123636-T-G

Position:

• chr14-35123636-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014672.4(PRORP):​c.391T>G​(p.Leu131Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRORP NM_014672.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.32

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09342396).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRORP	NM_014672.4	c.391T>G	p.Leu131Val	missense_variant	2/8	ENST00000534898.9	NP_055487.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRORP	ENST00000534898.9	c.391T>G	p.Leu131Val	missense_variant	2/8	1	NM_014672.4	ENSP00000440915.2
ENSG00000258790	ENST00000557565.1	n.391T>G		non_coding_transcript_exon_variant	2/15	2		ENSP00000454657.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 15, 2024

The c.391T>G (p.L131V) alteration is located in exon 2 (coding exon 1) of the KIAA0391 gene. This alteration results from a T to G substitution at nucleotide position 391, causing the leucine (L) at amino acid position 131 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0037	.;.;T;.
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.43	T;.;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.093	T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.68	.;.;N;.
REVEL	Benign	0.14
Sift	Benign	0.035	.;.;D;.
Sift4G	Benign	0.33	T;T;T;T
Polyphen		0.020	.;B;B;B
Vest4		0.16
MutPred		0.48		.;Loss of ubiquitination at K128 (P = 0.1423);Loss of ubiquitination at K128 (P = 0.1423);Loss of ubiquitination at K128 (P = 0.1423);
MVP		0.43
MPC		0.18
ClinPred		0.18	T
GERP RS		5.3
Varity_R		0.10
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-35592842;