6-30345468-C-T

Variant names:

• chr6-30345468-C-T
• NM_024839.4:c.159-23C>T

Variant summary

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

The NM_001199120.3(RPP21):​c.160C>T​(p.Pro54Ser) variant causes a missense, splice region 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. 14/19 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: RPP21 NM_001199120.3 missense, splice_region
• Scores: Splicing: ADA: 0.00008555
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.983

Genes affected

RPP21 (HGNC:21300): (ribonuclease P/MRP subunit p21) RPP21 is a protein subunit of nuclear ribonuclease P, which processes the 5-prime leader sequence of precursor tRNAs (Jarrous et al., 2001 [PubMed 11497433]).[supplied by OMIM, Jan 2009]

TRIM39-RPP21 (HGNC:38845): (TRIM39-RPP21 readthrough) This locus represents naturally occurring read-through transcription between the neighboring TRIM39 (tripartite motif-containing 39) and RPP21 (ribonuclease P/MRP 21kDa subunit) genes on chromosome 6. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Nov 2010]

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=0.16407177).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPP21	NM_024839.4	c.159-23C>T		intron_variant	Intron 2 of 4	ENST00000442966.7	NP_079115.1
RPP21	NM_001199120.3	c.160C>T	p.Pro54Ser	missense_variant, splice_region_variant	Exon 3 of 5		NP_001186049.1
TRIM39-RPP21	NM_001199119.1	c.1206-23C>T		intron_variant	Intron 7 of 9		NP_001186048.1
RPP21	NM_001199121.3	c.159-23C>T		intron_variant	Intron 2 of 4		NP_001186050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPP21	ENST00000442966.7	c.159-23C>T		intron_variant	Intron 2 of 4	1	NM_024839.4	ENSP00000403833.2
TRIM39-RPP21	ENST00000623385.3	c.1206-23C>T		intron_variant	Intron 8 of 10	5		ENSP00000485378.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.160C>T (p.P54S) alteration is located in exon 3 (coding exon 3) of the RPP21 gene. This alteration results from a C to T substitution at nucleotide position 160, causing the proline (P) at amino acid position 54 to be replaced by a serine (S). 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
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.4
DANN	Benign	0.90
Eigen	Benign	0.057
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.062	N
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	0.30	N
REVEL	Benign	0.012
Sift	Benign	0.88	T
Sift4G	Benign	0.57	T
Vest4		0.14
MutPred		0.41		Gain of phosphorylation at P54 (P = 0.0062);
MVP		0.76
MPC		0.53
ClinPred		0.061	T
GERP RS		-0.31
BranchPoint Hunter		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000086
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.010		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: chr6-30313245;