rs759913983

Variant names:

• chr11-6601263-C-A
• rs759913983
• NM_015324.4:c.803G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-6601263-C-A
• chr11-6601263-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015324.4(RRP8):​c.803G>T​(p.Arg268Leu) 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. 13/22 in silico tools predict a benign 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. R268H) 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: 2.08
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38209838).

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.803G>T	p.Arg268Leu	missense	Exon 3 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.803G>T	p.Arg268Leu	missense	Exon 3 of 7	ENSP00000254605.6	O43159
	RRP8	ENST00000874194.1		c.803G>T	p.Arg268Leu	missense	Exon 3 of 7	ENSP00000544253.1
	RRP8	ENST00000534343.1	TSL:2	c.100-488G>T		intron	N/A	ENSP00000436960.1	E9PPP6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.1
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.13
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.056	T
Polyphen		0.033	B
Vest4		0.57
MutPred		0.53		Loss of helix (P = 0.0041)
MVP		0.53
MPC		0.024
ClinPred		0.98	D
GERP RS		3.7
Varity_R		0.63
gMVP		0.61
Mutation Taster		=40/60	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs759913983; hg19: chr11-6622493;