Genetic Variant NM_016563.4:c.23C>T (chr15-65067813-G-A) – 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.23C>T(p.Pro8Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000703 in 1,422,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

RASL12
NM_016563.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.51

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=0.31140286).

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.23C>T	p.Pro8Leu	missense	Exon 1 of 5	NP_057647.1	Q9NYN1-1
RASL12	NM_001307930.2		c.23C>T	p.Pro8Leu	missense	Exon 1 of 4	NP_001294859.1	Q9NYN1-3
RASL12	NM_001379429.1		c.71-2540C>T		intron	N/A	NP_001366358.1	Q9NYN1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RASL12	ENST00000220062.9	TSL:1 MANE Select	c.23C>T	p.Pro8Leu	missense	Exon 1 of 5	ENSP00000220062.4	Q9NYN1-1
RASL12	ENST00000421977.7	TSL:2	c.23C>T	p.Pro8Leu	missense	Exon 1 of 4	ENSP00000390028.3	Q9NYN1-3
RASL12	ENST00000434605.2	TSL:2	c.71-2540C>T		intron	N/A	ENSP00000412787.2	Q9NYN1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000552

AC:

AN:

181074

AF XY:

0.00000989

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:

0.0000129

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.03e-7

AC:

AN:

1422268

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

705834

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30208

American (AMR)

AF:

0.00

AC:

AN:

40858

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24568

East Asian (EAS)

AF:

0.00

AC:

AN:

36060

South Asian (SAS)

AF:

0.00

AC:

AN:

82044

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48226

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5632

European-Non Finnish (NFE)

AF:

9.12e-7

AC:

AN:

1096014

Other (OTH)

AF:

0.00

AC:

AN:

58658

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

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

0.15

BayesDel_addAF

Uncertain

0.031

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.83

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.31

MetaSVM

Uncertain

-0.038

MutationAssessor

Benign

1.6

PhyloP100

4.5

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.2

REVEL

Benign

0.27

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.016

Polyphen

0.24

Vest4

0.35

MutPred

0.33

Gain of MoRF binding (P = 0.0289)

MVP

0.88

MPC

0.25

ClinPred

0.43

GERP RS

4.5

PromoterAI

0.028

Neutral

(source)

Varity_R

0.23

gMVP

0.48

Mutation Taster

=77/23

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over