8-66429442-C-T

Variant names:

• chr8-66429442-C-T
• rs375781629
• NM_015169.4:c.311C>T

Variant summary

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

The NM_015169.4(RRS1):​c.311C>T​(p.Pro104Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000713 in 1,403,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P104S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: RRS1 NM_015169.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.41
• Publications: 0 publications found

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]

RRS1-DT (HGNC:50465): (RRS1 divergent transcript)

LOC102724687 (HGNC:):

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=0.33480012).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015169.4. 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
	RRS1	NM_015169.4	MANE Select	c.311C>T	p.Pro104Leu	missense	Exon 1 of 1	NP_055984.1	Q15050

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRS1	ENST00000320270.4	TSL:6 MANE Select	c.311C>T	p.Pro104Leu	missense	Exon 1 of 1	ENSP00000322396.2	Q15050
	RRS1-DT	ENST00000659008.1		n.87+2842G>A		intron	N/A
	RRS1-DT	ENST00000734543.1		n.116+2842G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.13e-7 AC: 1 AN: 1403152 Hom.: 0 Cov.: 31 AF XY: 0.00000144 AC XY: 1 AN XY: 692844

African (AFR) AF: 0.00 AC: 0 AN: 31824

American (AMR) AF: 0.00 AC: 0 AN: 35942

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25200

East Asian (EAS) AF: 0.00 AC: 0 AN: 36038

South Asian (SAS) AF: 0.00 AC: 0 AN: 80224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5540

European-Non Finnish (NFE) AF: 9.24e-7 AC: 1 AN: 1081768

Other (OTH) AF: 0.00 AC: 0 AN: 58204

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		5.4
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.021	D
Polyphen		0.56	P
Vest4		0.15
MutPred		0.48		Gain of MoRF binding (P = 0.0403)
MVP		0.35
MPC		1.1
ClinPred		0.99	D
GERP RS		6.0
PromoterAI		-0.033	Neutral
Varity_R		0.62
gMVP		0.53
Mutation Taster		=51/49	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: rs375781629; hg19: chr8-67341677;