chr14-35123523-G-C

Position:

• chr14-35123523-G-C

Variant summary

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

The NM_014672.4(PRORP):​c.278G>C​(p.Arg93Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRORP NM_014672.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.74

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=0.23566103).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRORP	NM_014672.4	c.278G>C	p.Arg93Thr	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.278G>C	p.Arg93Thr	missense_variant	2/8	1	NM_014672.4	ENSP00000440915.2
ENSG00000258790	ENST00000557565.1	n.278G>C		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

Aug 28, 2024

The c.278G>C (p.R93T) alteration is located in exon 2 (coding exon 1) of the KIAA0391 gene. This alteration results from a G to C substitution at nucleotide position 278, causing the arginine (R) at amino acid position 93 to be replaced by a threonine (T). 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	0.27
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.0065	.;T;.
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.75	.;T;T
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.70	T
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.1	.;N;.
REVEL	Benign	0.15
Sift	Benign	0.049	.;D;.
Sift4G	Uncertain	0.057	T;D;T
Polyphen		0.64	P;P;P
Vest4		0.21
MutPred		0.43		Gain of ubiquitination at K91 (P = 0.0542);Gain of ubiquitination at K91 (P = 0.0542);Gain of ubiquitination at K91 (P = 0.0542);
MVP		0.73
MPC		0.81
ClinPred		0.92	D
GERP RS		4.2
Varity_R		0.19
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: chr14-35592729;