Genetic Variant NM_023940.3:c.94C>T (chr4-52862601-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_023940.3(RASL11B):c.94C>T(p.Arg32Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000484 in 1,446,182 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

RASL11B
NM_023940.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0520

Publications

0 publications found

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]

RASL11B links:

ENSG00000305969 (HGNC:):

ENSG00000305969 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.775

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023940.3. 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
	RASL11B	NM_023940.3	MANE Select	c.94C>T	p.Arg32Cys	missense	Exon 1 of 4	NP_076429.1	Q9BPW5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RASL11B	ENST00000248706.5	TSL:1 MANE Select	c.94C>T	p.Arg32Cys	missense	Exon 1 of 4	ENSP00000248706.3	Q9BPW5
RASL11B	ENST00000515677.1	TSL:3	n.270C>T		non_coding_transcript_exon	Exon 1 of 2
ENSG00000305969	ENST00000814437.1		n.209G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

219232

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000484

AC:

AN:

1446182

Hom.:

Cov.:

AF XY:

0.00000417

AC XY:

AN XY:

719300

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32418

American (AMR)

AF:

0.00

AC:

AN:

43972

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25676

East Asian (EAS)

AF:

0.00

AC:

AN:

39028

South Asian (SAS)

AF:

0.00

AC:

AN:

85430

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45866

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.00000541

AC:

AN:

1108202

Other (OTH)

AF:

0.0000167

AC:

AN:

59854

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.17

Eigen

Benign

0.062

Eigen_PC

Benign

0.040

FATHMM_MKL

Benign

0.33

LIST_S2

Uncertain

0.86

M_CAP

Pathogenic

0.43

MetaRNN

Pathogenic

0.77

MetaSVM

Uncertain

-0.0033

MutationAssessor

Benign

0.0

PhyloP100

0.052

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.54

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.66

MutPred

0.58

Loss of MoRF binding (P = 0.008)

MVP

0.75

MPC

1.2

ClinPred

0.83

GERP RS

4.3

PromoterAI

-0.0081

Neutral

(source)

Varity_R

0.60

gMVP

0.78

Mutation Taster

=45/55

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over