chr16-11841777-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_015659.3(RSL1D1):​c.773C>G​(p.Ser258Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

RSL1D1
NM_015659.3 missense

Scores

8
8
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.22
Variant links:
Genes affected
RSL1D1 (HGNC:24534): (ribosomal L1 domain containing 1) Enables mRNA 3'-UTR binding activity and mRNA 5'-UTR binding activity. Involved in regulation of apoptotic process and regulation of cellular senescence. Acts upstream of or within regulation of protein localization. Located in chromosome and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.85

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RSL1D1NM_015659.3 linkuse as main transcriptc.773C>G p.Ser258Trp missense_variant 7/9 ENST00000571133.6 NP_056474.2 O76021-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RSL1D1ENST00000571133.6 linkuse as main transcriptc.773C>G p.Ser258Trp missense_variant 7/91 NM_015659.3 ENSP00000460871.1 O76021-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 10, 2024The c.773C>G (p.S258W) alteration is located in exon 7 (coding exon 7) of the RSL1D1 gene. This alteration results from a C to G substitution at nucleotide position 773, causing the serine (S) at amino acid position 258 to be replaced by a tryptophan (W). 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
Pathogenic
0.90
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.19
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.38
T;.;T
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.85
D;D;D
MetaSVM
Uncertain
0.10
D
MutationAssessor
Pathogenic
3.7
H;.;.
PrimateAI
Benign
0.47
T
PROVEAN
Pathogenic
-6.2
.;D;.
REVEL
Uncertain
0.54
Sift
Pathogenic
0.0
.;D;.
Sift4G
Pathogenic
0.0010
D;.;.
Polyphen
1.0
D;.;.
Vest4
0.93
MutPred
0.62
Gain of catalytic residue at S258 (P = 0.0011);.;.;
MVP
0.88
MPC
0.085
ClinPred
1.0
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.72
gMVP
0.80

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: chr16-11935634; API