Variant chr15-65055097-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000220062.9(RASL12):c.603G>C(p.Glu201Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RASL12
ENST00000220062.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.574

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07204321).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASL12	NM_016563.4 linkuse as main transcript	c.603G>C	p.Glu201Asp	missense_variant	5/5	ENST00000220062.9	NP_057647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASL12	ENST00000220062.9 linkuse as main transcript	c.603G>C	p.Glu201Asp	missense_variant	5/5	1	NM_016563.4	ENSP00000220062	P1	Q9NYN1-1
RASL12	ENST00000434605.2 linkuse as main transcript	c.570G>C	p.Glu190Asp	missense_variant	5/5	2		ENSP00000412787		Q9NYN1-2
RASL12	ENST00000421977.7 linkuse as main transcript	c.546G>C	p.Glu182Asp	missense_variant	4/4	2		ENSP00000390028		Q9NYN1-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459216

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725792

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2022

The c.603G>C (p.E201D) alteration is located in exon 5 (coding exon 5) of the RASL12 gene. This alteration results from a G to C substitution at nucleotide position 603, causing the glutamic acid (E) at amino acid position 201 to be replaced by an aspartic acid (D). 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

0.076

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

6.1

DANN

Uncertain

0.99

DEOGEN2

Benign

0.091

T;.;.

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.66

T;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.072

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.34

N;.;.

MutationTaster

Benign

0.98

N;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.17

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.46

T;T;T

Sift4G

Benign

0.44

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.050

MutPred

0.24

Gain of helix (P = 0.062);.;.;

MVP

0.62

MPC

0.20

ClinPred

0.23

GERP RS

0.39

Varity_R

0.051

gMVP

0.098

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over