Variant 17-35741138-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_033315.4(RASL10B):c.445A>C(p.Lys149Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

RASL10B
NM_033315.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.89

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.753

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RASL10B	NM_033315.4 linkuse as main transcript	c.445A>C	p.Lys149Gln	missense_variant	4/4	ENST00000603017.2	NP_201572.1
RASL10B	XM_047437043.1 linkuse as main transcript	c.622A>C	p.Lys208Gln	missense_variant	5/5		XP_047292999.1
RASL10B	XM_017025300.2 linkuse as main transcript	c.615+7A>C		splice_region_variant, intron_variant			XP_016880789.1
RASL10B	XR_934595.3 linkuse as main transcript	n.592A>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.445A>C	p.Lys149Gln	missense_variant	4/4	1	NM_033315.4	ENSP00000474230	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461196

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726912

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:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

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

Sep 29, 2023

The c.445A>C (p.K149Q) alteration is located in exon 4 (coding exon 3) of the RASL10B gene. This alteration results from a A to C substitution at nucleotide position 445, causing the lysine (K) at amino acid position 149 to be replaced by a glutamine (Q). 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

Uncertain

0.51

BayesDel_addAF

Uncertain

0.087

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.070

MetaRNN

Pathogenic

0.75

MetaSVM

Uncertain

-0.21

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.87

Sift4G

Uncertain

0.014

Polyphen

0.99

Vest4

0.61

MutPred

0.40

Loss of methylation at K149 (P = 0.0145);

MVP

0.90

ClinPred

0.99

GERP RS

4.9

Varity_R

0.39

gMVP

0.81

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