Variant 22-29315051-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006477.5(RASL10A):c.196G>A(p.Gly66Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000294 in 1,362,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

RASL10A
NM_006477.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0750

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:

RASL10A (HGNC:):

RASL10A 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=0.10718265).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASL10A	NM_006477.5 linkuse as main transcript	c.196G>A	p.Gly66Ser	missense_variant	1/3	ENST00000216101.7	NP_006468.1	Q92737-1A0A024R1C8
RASL10A	XM_011529822.1 linkuse as main transcript	c.279+814G>A		intron_variant			XP_011528124.1
RASL10A	XM_011529823.2 linkuse as main transcript	c.76-1064G>A		intron_variant			XP_011528125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RASL10A	ENST00000216101.7 linkuse as main transcript	c.196G>A	p.Gly66Ser	missense_variant	1/3	1	NM_006477.5	ENSP00000216101.6	Q92737-1
RASL10A	ENST00000401450.3 linkuse as main transcript	c.196G>A	p.Gly66Ser	missense_variant	1/2	2		ENSP00000386095.3	Q92737-2
RASL10A	ENST00000608559.1 linkuse as main transcript	n.372-1064G>A		intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000294

AC:

AN:

1362400

Hom.:

Cov.:

AF XY:

0.00000298

AC XY:

AN XY:

671214

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:

0.00000375

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 11, 2024

The c.196G>A (p.G66S) alteration is located in exon 1 (coding exon 1) of the RASL10A gene. This alteration results from a G to A substitution at nucleotide position 196, causing the glycine (G) at amino acid position 66 to be replaced by a serine (S). 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

0.093

BayesDel_addAF

Benign

-0.084

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.15

.;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.53

T;T

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

0.41

N;N

PrimateAI

Uncertain

0.64

PROVEAN

Benign

0.15

N;N

REVEL

Benign

0.14

Sift

Benign

0.40

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.87

.;P

Vest4

0.16

MutPred

0.35

Gain of glycosylation at G66 (P = 0.0072);Gain of glycosylation at G66 (P = 0.0072);

MVP

0.28

MPC

1.2

ClinPred

0.14

GERP RS

1.9

Varity_R

0.034

gMVP

0.35

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