Variant 17-35741246-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000603017.2(RASL10B):c.553G>C(p.Val185Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000251 in 1,592,180 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: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RASL10B
ENST00000603017.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.75

Variant links:

Genes affected

RASL10B (HGNC:30295): (RAS like family 10 member B) Predicted to enable G protein activity and GTP binding activity. Predicted to be involved in positive regulation of peptide hormone secretion and regulation of systemic arterial blood pressure by atrial natriuretic peptide. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

RASL10B links:

RASL10B (HGNC:):

RASL10B links:

Genome browser will be placed here

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=0.16597337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASL10B	NM_033315.4 linkuse as main transcript	c.553G>C	p.Val185Leu	missense_variant	4/4	ENST00000603017.2	NP_201572.1	Q96S79
RASL10B	XM_047437043.1 linkuse as main transcript	c.730G>C	p.Val244Leu	missense_variant	5/5		XP_047292999.1
RASL10B	XM_017025300.2 linkuse as main transcript	c.615+115G>C		intron_variant			XP_016880789.1
RASL10B	XR_934595.3 linkuse as main transcript	n.700G>C		non_coding_transcript_exon_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASL10B	ENST00000603017.2 linkuse as main transcript	c.553G>C	p.Val185Leu	missense_variant	4/4	1	NM_033315.4	ENSP00000474230.1		Q96S79

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1439952

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

714320

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:

0.00000272

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Dec 27, 2023

The c.553G>C (p.V185L) alteration is located in exon 4 (coding exon 3) of the RASL10B gene. This alteration results from a G to C substitution at nucleotide position 553, causing the valine (V) at amino acid position 185 to be replaced by a leucine (L). 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

0.14

BayesDel_addAF

Benign

-0.019

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.011

Eigen

Benign

-0.032

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.63

M_CAP

Benign

0.050

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.54

MutationAssessor

Benign

-0.97

MutationTaster

Benign

0.98

PrimateAI

Pathogenic

0.93

Sift4G

Benign

0.31

Polyphen

0.24

Vest4

0.26

MutPred

0.38

Loss of MoRF binding (P = 0.0944);

MVP

0.87

ClinPred

1.0

GERP RS

5.4

Varity_R

0.18

gMVP

0.76

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over