chr6-30345563-G-T

Variant names:

• chr6-30345563-G-T
• NM_024839.4:c.231G>T
• RPP21 p.Gln77His

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.231G>T​(p.Gln77His) 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. 12/21 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: 27)
• Consequence: RPP21 NM_024839.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.08
• 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: Computational evidence support a benign effect (MetaRNN=0.13699418).

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.231G>T	p.Gln77His	missense	Exon 3 of 5	NP_079115.1	Q9H633-1
	TRIM39-RPP21	NM_001199119.1		c.1278G>T	p.Gln426His	missense	Exon 8 of 10	NP_001186048.1	A0A096LP39
	RPP21	NM_001199120.3		c.255G>T	p.Gln85His	missense	Exon 3 of 5	NP_001186049.1	Q9H633-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPP21	ENST00000442966.7	TSL:1 MANE Select	c.231G>T	p.Gln77His	missense	Exon 3 of 5	ENSP00000403833.2	Q9H633-1
	TRIM39-RPP21	ENST00000623385.3	TSL:5	c.1278G>T	p.Gln426His	missense	Exon 9 of 11	ENSP00000485378.1	A0A096LP39
	RPP21	ENST00000436442.2	TSL:1	c.231G>T	p.Gln77His	missense	Exon 3 of 5	ENSP00000397778.2	Q9H633-3

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	0.081
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.1
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.043
Sift	Benign	0.46	T
Sift4G	Benign	0.061	T
PromoterAI		0.037	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.45
Mutation Taster		=97/3	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-30313340;