NM_024839.4:c.159-23C>T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024839.4(RPP21):​c.159-23C>T variant causes a intron 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. Variant has been reported in ClinVar as Uncertain significance (★). There are indicators that this mutation may affect the branch point..

• Frequency: Genomes: not found (cov: 31)
• Consequence: RPP21 NM_024839.4 intron
• Scores: Splicing: ADA: 0.00008555
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.983
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (MetaRNN=0.16407177).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024839.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPP21	NM_024839.4	MANE Select	c.159-23C>T		intron	N/A	NP_079115.1	Q9H633-1
	RPP21	NM_001199120.3		c.160C>T	p.Pro54Ser	missense splice_region	Exon 3 of 5	NP_001186049.1	Q9H633-4
	TRIM39-RPP21	NM_001199119.1		c.1206-23C>T		intron	N/A	NP_001186048.1	A0A096LP39

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPP21	ENST00000442966.7	TSL:1 MANE Select	c.159-23C>T		intron	N/A	ENSP00000403833.2	Q9H633-1
	TRIM39-RPP21	ENST00000623385.3	TSL:5	c.1206-23C>T		intron	N/A	ENSP00000485378.1	A0A096LP39
	RPP21	ENST00000436442.2	TSL:1	c.159-23C>T		intron	N/A	ENSP00000397778.2	Q9H633-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
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
PhyloP100		-0.98
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
PromoterAI		0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.31
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

hg19: chr6-30313245;