rs200309492

Variant names:

• chr11-6600505-C-A
• rs200309492
• NM_015324.4:c.1232G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-6600505-C-A
• chr11-6600505-C-G
• chr11-6600505-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_015324.4(RRP8):​c.1232G>T​(p.Gly411Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G411D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RRP8 NM_015324.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.80
• Publications: 0 publications found

Genes affected

RRP8 (HGNC:29030): (ribosomal RNA processing 8) Enables methylated histone binding activity. Involved in several processes, including cellular response to glucose starvation; intrinsic apoptotic signaling pathway by p53 class mediator; and regulation of gene expression. Located in several cellular components, including cytosol; nuclear lumen; and rDNA heterochromatin. Part of chromatin silencing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.972

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015324.4. 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
	RRP8	NM_015324.4	MANE Select	c.1232G>T	p.Gly411Val	missense	Exon 6 of 7	NP_056139.1	O43159

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRP8	ENST00000254605.11	TSL:1 MANE Select	c.1232G>T	p.Gly411Val	missense	Exon 6 of 7	ENSP00000254605.6	O43159
	RRP8	ENST00000874194.1		c.1232G>T	p.Gly411Val	missense	Exon 6 of 7	ENSP00000544253.1
	RRP8	ENST00000534343.1	TSL:2	c.284G>T	p.Gly95Val	missense	Exon 3 of 4	ENSP00000436960.1	E9PPP6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Uncertain	0.12	D
MutationAssessor	Pathogenic	3.7	H
PhyloP100		6.8
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-8.7	D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.99
MutPred		0.85		Gain of helix (P = 0.0117)
MVP		0.89
MPC		0.14
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.98
gMVP		0.83
Mutation Taster		=19/81	disease causing

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

Other links and lift over

dbSNP: rs200309492; hg19: chr11-6621735;