chr8-66429454-C-T

Position:

• chr8-66429454-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015169.4(RRS1):​c.323C>T​(p.Pro108Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: RRS1 NM_015169.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.29

Genes affected

RRS1 (HGNC:17083): (ribosome biogenesis regulator 1 homolog) Enables 5S rRNA binding activity. Involved in several processes, including mitotic metaphase plate congression; protein localization to nucleolus; and ribosomal large subunit assembly. Located in condensed nuclear chromosome; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000287127 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30841476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRS1	NM_015169.4	c.323C>T	p.Pro108Leu	missense_variant	1/1	ENST00000320270.4	NP_055984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRS1	ENST00000320270.4	c.323C>T	p.Pro108Leu	missense_variant	1/1	6	NM_015169.4	ENSP00000322396.2
ENSG00000287127	ENST00000659008.1	n.87+2830G>A		intron_variant

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2023

The c.323C>T (p.P108L) alteration is located in exon 1 (coding exon 1) of the RRS1 gene. This alteration results from a C to T substitution at nucleotide position 323, causing the proline (P) at amino acid position 108 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.8	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.14	T
Polyphen		0.58	P
Vest4		0.24
MutPred		0.57		Loss of glycosylation at P108 (P = 0.0079);
MVP		0.15
MPC		0.57
ClinPred		0.98	D
GERP RS		6.0
Varity_R		0.44
gMVP		0.50

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-67341689;