Genetic Variant RASL10A:p.Cys159Tyr (chr22-29313437-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_006477.5(RASL10A):c.476G>A(p.Cys159Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000195 in 1,541,024 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: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RASL10A
NM_006477.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.80

Variant links:

Genes affected

RASL10A (HGNC:16954): (RAS like family 10 member A) Predicted to enable GTPase activity. Predicted to be involved in small GTPase mediated signal transduction. Predicted to be located in nucleolus and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

RASL10A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.938

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASL10A	NM_006477.5 link	c.476G>A	p.Cys159Tyr	missense_variant	Exon 3 of 3	ENST00000216101.7	NP_006468.1	Q92737-1A0A024R1C8
RASL10A	XM_011529822.1 link	c.536G>A	p.Cys179Tyr	missense_variant	Exon 4 of 4		XP_011528124.1
RASL10A	XM_011529823.2 link	c.332G>A	p.Cys111Tyr	missense_variant	Exon 3 of 3		XP_011528125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RASL10A	ENST00000216101.7 link	c.476G>A	p.Cys159Tyr	missense_variant	Exon 3 of 3	1	NM_006477.5	ENSP00000216101.6	Q92737-1
RASL10A	ENST00000401450 link	c.*422G>A		3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000386095.3	Q92737-2
RASL10A	ENST00000474590.1 link	n.*98G>A		downstream_gene_variant		2
RASL10A	ENST00000608559.1 link	n.*66G>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152240

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:

0.00000144

AC:

AN:

1388784

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

685698

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:

0.00000185

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.00

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

Mar 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.476G>A (p.C159Y) alteration is located in exon 3 (coding exon 3) of the RASL10A gene. This alteration results from a G to A substitution at nucleotide position 476, causing the cysteine (C) at amino acid position 159 to be replaced by a tyrosine (Y). 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

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.41

BayesDel_noAF

Pathogenic

0.34

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.71

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

M_CAP

Pathogenic

0.45

MetaRNN

Pathogenic

0.94

MetaSVM

Uncertain

0.59

MutationAssessor

Pathogenic

3.7

PrimateAI

Pathogenic

0.98

PROVEAN

Pathogenic

-9.2

REVEL

Pathogenic

0.89

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.79

MutPred

0.76

Gain of MoRF binding (P = 0.237);

MVP

0.81

MPC

3.1

ClinPred

1.0

GERP RS

4.2

Varity_R

0.95

gMVP

0.92

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