4-52865768-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_023940.3(RASL11B):​c.710C>T​(p.Ala237Val) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

RASL11B
NM_023940.3 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.70
Variant links:
Genes affected
RASL11B (HGNC:23804): (RAS like family 11 member B) Predicted to enable G protein activity; GTP binding activity; and transforming growth factor beta receptor binding activity. Predicted to act upstream of or within negative regulation of transforming growth factor beta receptor signaling pathway. [provided by Alliance of Genome Resources, Apr 2022]
LINC01618 (HGNC:27195): (long intergenic non-protein coding RNA 1618)

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ACMG classification

Classification made for transcript

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=0.37263995).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RASL11BNM_023940.3 linkc.710C>T p.Ala237Val missense_variant Exon 4 of 4 ENST00000248706.5 NP_076429.1 Q9BPW5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RASL11BENST00000248706.5 linkc.710C>T p.Ala237Val missense_variant Exon 4 of 4 1 NM_023940.3 ENSP00000248706.3 Q9BPW5
RASL11BENST00000505041.1 linkn.702C>T non_coding_transcript_exon_variant Exon 3 of 3 3
LINC01618ENST00000650700.1 linkn.1556C>T non_coding_transcript_exon_variant Exon 11 of 11
LINC01618ENST00000652441.1 linkn.1071C>T non_coding_transcript_exon_variant Exon 6 of 6

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 04, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.710C>T (p.A237V) alteration is located in exon 4 (coding exon 4) of the RASL11B gene. This alteration results from a C to T substitution at nucleotide position 710, causing the alanine (A) at amino acid position 237 to be replaced by a valine (V). 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
0.17
BayesDel_addAF
Benign
0.0035
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.064
T
Eigen
Benign
0.12
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.37
T
MetaSVM
Benign
-0.77
T
MutationAssessor
Benign
0.87
L
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
-2.0
N
REVEL
Benign
0.17
Sift
Benign
0.20
T
Sift4G
Benign
0.25
T
Polyphen
0.40
B
Vest4
0.69
MutPred
0.27
Gain of glycosylation at S239 (P = 0.0435);
MVP
0.75
MPC
0.58
ClinPred
0.50
T
GERP RS
5.9
Varity_R
0.23
gMVP
0.60

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: chr4-53731935; API