Variant chr17-35735356-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000603017.2(RASL10B):c.172C>G(p.Leu58Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000812 in 1,614,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000082 ( 0 hom. )

Consequence

RASL10B
ENST00000603017.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.33

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32064414).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASL10B	NM_033315.4 linkuse as main transcript	c.172C>G	p.Leu58Val	missense_variant	2/4	ENST00000603017.2	NP_201572.1	Q96S79
RASL10B	XM_047437043.1 linkuse as main transcript	c.349C>G	p.Leu117Val	missense_variant	3/5		XP_047292999.1
RASL10B	XM_017025300.2 linkuse as main transcript	c.349C>G	p.Leu117Val	missense_variant	2/5		XP_016880789.1
RASL10B	XR_934595.3 linkuse as main transcript	n.319C>G		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASL10B	ENST00000603017.2 linkuse as main transcript	c.172C>G	p.Leu58Val	missense_variant	2/4	1	NM_033315.4	ENSP00000474230.1		Q96S79
RASL10B	ENST00000603498.1 linkuse as main transcript	n.20C>G		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.0000722

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000482

AC:

AN:

248934

Hom.:

AF XY:

0.0000668

AC XY:

AN XY:

134796

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000899

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000821

AC:

120

AN:

1461842

Hom.:

Cov.:

AF XY:

0.0000784

AC XY:

AN XY:

727224

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:

0.000105

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0000482

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:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

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 29, 2024

The c.172C>G (p.L58V) alteration is located in exon 2 (coding exon 1) of the RASL10B gene. This alteration results from a C to G substitution at nucleotide position 172, causing the leucine (L) at amino acid position 58 to be replaced by a valine (V). 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

0.13

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.16

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.85

M_CAP

Benign

0.018

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.56

PrimateAI

Uncertain

0.68

Sift4G

Benign

0.67

Polyphen

0.0070

Vest4

0.37

MVP

0.83

ClinPred

0.034

GERP RS

4.2

Varity_R

0.093

gMVP

0.43

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