4-52865395-G-T

Variant names:

• chr4-52865395-G-T
• NM_023940.3:c.337G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_023940.3(RASL11B):​c.337G>T​(p.Ala113Ser) 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: 33)
• Consequence: RASL11B NM_023940.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.46

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)

ACMG classification

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, 0.938

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASL11B	NM_023940.3	c.337G>T	p.Ala113Ser	missense_variant	Exon 4 of 4	ENST00000248706.5	NP_076429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASL11B	ENST00000248706.5	c.337G>T	p.Ala113Ser	missense_variant	Exon 4 of 4	1	NM_023940.3	ENSP00000248706.3
RASL11B	ENST00000505041.1	n.329G>T		non_coding_transcript_exon_variant	Exon 3 of 3	3
LINC01618	ENST00000650700.1	n.1183G>T		non_coding_transcript_exon_variant	Exon 11 of 11
LINC01618	ENST00000652441.1	n.698G>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

Submissions by phenotype

not specified Uncertain:1

Nov 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.337G>T (p.A113S) alteration is located in exon 4 (coding exon 4) of the RASL11B gene. This alteration results from a G to T substitution at nucleotide position 337, causing the alanine (A) at amino acid position 113 to be replaced by a serine (S). 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	Uncertain	0.38
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	0.54	D
MutationAssessor	Pathogenic	3.0	M
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.92	N
REVEL	Uncertain	0.61
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.020	D
Polyphen		1.0	D
Vest4		0.75
MutPred		0.80		Loss of catalytic residue at A113 (P = 0.0326);
MVP		0.82
MPC		1.1
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.26
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: chr4-53731562; COSMIC: COSV99954543; COSMIC: COSV99954543;