Genetic Variant RASL12:p.Arg82Lys (chr15-65058607-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_016563.4(RASL12):c.245G>A(p.Arg82Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000781 in 1,408,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R82G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000078 ( 0 hom. )

Consequence

RASL12
NM_016563.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.02

Publications

0 publications found

Variant links:

Genes affected

RASL12 (HGNC:30289): (RAS like family 12) Predicted to enable GDP binding activity; GTP binding activity; and GTPase activity. Predicted to be involved in signal transduction. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

RASL12 links:

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ACMG classification

Classification was made for transcript

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=0.32769853).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016563.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RASL12	NM_016563.4	MANE Select	c.245G>A	p.Arg82Lys	missense	Exon 4 of 5	NP_057647.1	Q9NYN1-1
RASL12	NM_001379429.1		c.212G>A	p.Arg71Lys	missense	Exon 4 of 5	NP_001366358.1	Q9NYN1-2
RASL12	NM_001307930.2		c.188G>A	p.Arg63Lys	missense	Exon 3 of 4	NP_001294859.1	Q9NYN1-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RASL12	ENST00000220062.9	TSL:1 MANE Select	c.245G>A	p.Arg82Lys	missense	Exon 4 of 5	ENSP00000220062.4	Q9NYN1-1
RASL12	ENST00000434605.2	TSL:2	c.212G>A	p.Arg71Lys	missense	Exon 4 of 5	ENSP00000412787.2	Q9NYN1-2
RASL12	ENST00000421977.7	TSL:2	c.188G>A	p.Arg63Lys	missense	Exon 3 of 4	ENSP00000390028.3	Q9NYN1-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000443

AC:

AN:

225966

AF XY:

0.00

show subpopulations

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:

0.00000781

AC:

AN:

1408674

Hom.:

Cov.:

AF XY:

0.0000101

AC XY:

AN XY:

695172

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32270

American (AMR)

AF:

0.00

AC:

AN:

41268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24406

East Asian (EAS)

AF:

0.00

AC:

AN:

37962

South Asian (SAS)

AF:

0.000137

AC:

AN:

80360

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52144

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5578

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1076932

Other (OTH)

AF:

0.00

AC:

AN:

57754

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

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.:

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

Benign

0.096

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.25

Eigen

Benign

-0.027

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.73

M_CAP

Benign

0.030

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.37

MutationAssessor

Benign

1.2

PhyloP100

3.0

PrimateAI

Benign

0.47

PROVEAN

Benign

0.15

REVEL

Benign

0.22

Sift

Benign

0.59

Sift4G

Benign

0.93

Polyphen

0.0010

Vest4

0.36

MutPred

0.61

Gain of methylation at R82 (P = 0.0163)

MVP

0.74

MPC

0.22

ClinPred

0.30

GERP RS

4.4

Varity_R

0.25

gMVP

0.53

Mutation Taster

=81/19

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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