Genetic Variant RASL10A:p.Arg137Leu (chr22-29313503-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

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

The NM_006477.5(RASL10A):c.410G>T(p.Arg137Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RASL10A
NM_006477.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.52

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:

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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, 0.837

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASL10A	NM_006477.5 link	c.410G>T	p.Arg137Leu	missense_variant	Exon 3 of 3	ENST00000216101.7	NP_006468.1	Q92737-1A0A024R1C8
RASL10A	XM_011529822.1 link	c.470G>T	p.Arg157Leu	missense_variant	Exon 4 of 4		XP_011528124.1
RASL10A	XM_011529823.2 link	c.266G>T	p.Arg89Leu	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.410G>T	p.Arg137Leu	missense_variant	Exon 3 of 3	1	NM_006477.5	ENSP00000216101.6	Q92737-1
RASL10A	ENST00000401450 link	c.*356G>T		3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000386095.3	Q92737-2
RASL10A	ENST00000608559.1 link	n.562G>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 3 of 3	5
RASL10A	ENST00000474590.1 link	n.*32G>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1416158

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

702242

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:

0.00

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

Jan 17, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.410G>T (p.R137L) alteration is located in exon 3 (coding exon 3) of the RASL10A gene. This alteration results from a G to T substitution at nucleotide position 410, causing the arginine (R) at amino acid position 137 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

Uncertain

0.55

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

M_CAP

Pathogenic

0.46

MetaRNN

Pathogenic

0.84

MetaSVM

Uncertain

0.29

MutationAssessor

Uncertain

2.4

PrimateAI

Pathogenic

0.93

PROVEAN

Uncertain

-2.9

REVEL

Pathogenic

0.72

Sift

Benign

0.036

Sift4G

Benign

0.39

Polyphen

0.98

Vest4

0.70

MutPred

0.64

Loss of disorder (P = 0.0315);

MVP

0.28

MPC

2.2

ClinPred

0.99

GERP RS

5.0

Varity_R

0.54

gMVP

0.80

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

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