11-6600718-T-A

Variant names:

• chr11-6600718-T-A
• rs760883930
• NM_015324.4:c.1105A>T

Variant summary

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

The NM_015324.4(RRP8):​c.1105A>T​(p.Thr369Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,092 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T369A) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: RRP8 NM_015324.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.27
• Publications: 1 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRP8	NM_015324.4	c.1105A>T	p.Thr369Ser	missense_variant	Exon 5 of 7	ENST00000254605.11	NP_056139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRP8	ENST00000254605.11	c.1105A>T	p.Thr369Ser	missense_variant	Exon 5 of 7	1	NM_015324.4	ENSP00000254605.6

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152092 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152092 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74298

African (AFR) AF: 0.0000242 AC: 1 AN: 41400

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.6	M;.
PhyloP100		5.3
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Uncertain	0.31
Sift	Uncertain	0.018	D;D
Sift4G	Uncertain	0.020	D;T
Polyphen		0.94	P;.
Vest4		0.58
MutPred		0.86		Loss of catalytic residue at T369 (P = 0.073);.;
MVP		0.78
MPC		0.035
ClinPred		0.96	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.29
Mutation Taster		=79/21	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

Other links and lift over

dbSNP: rs760883930; hg19: chr11-6621948;