chr11-6600214-G-T

Variant names:

• chr11-6600214-G-T
• rs1202462843
• NM_015324.4:c.1303C>A

Variant summary

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

The NM_015324.4(RRP8):​c.1303C>A​(p.Pro435Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. P435A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RRP8 NM_015324.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.88
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.112965226).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRP8	NM_015324.4	c.1303C>A	p.Pro435Thr	missense_variant	Exon 7 of 7	ENST00000254605.11	NP_056139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRP8	ENST00000254605.11	c.1303C>A	p.Pro435Thr	missense_variant	Exon 7 of 7	1	NM_015324.4	ENSP00000254605.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455204 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 723856

African (AFR) AF: 0.00 AC: 0 AN: 32844

American (AMR) AF: 0.00 AC: 0 AN: 42858

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25790

East Asian (EAS) AF: 0.00 AC: 0 AN: 39620

South Asian (SAS) AF: 0.00 AC: 0 AN: 85228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53246

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109810

Other (OTH) AF: 0.00 AC: 0 AN: 60070

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Benign	0.87
DEOGEN2	Benign	0.0061	T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	0.024
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.
PhyloP100		2.9
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.72	N;N
REVEL	Benign	0.062
Sift	Uncertain	0.028	D;T
Sift4G	Benign	0.18	T;T
Polyphen		0.013	B;.
Vest4		0.16
MutPred		0.41		Loss of phosphorylation at T432 (P = 0.0818);.;
MVP		0.56
MPC		0.023
ClinPred		0.29	T
GERP RS		5.4
Varity_R		0.26
gMVP		0.17
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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

dbSNP: rs1202462843; hg19: chr11-6621444;