Genetic Variant RASL10A:p.Arg110His (chr22-29313878-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_006477.5(RASL10A):c.329G>A(p.Arg110His) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R110L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RASL10A
NM_006477.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.66

Publications

0 publications found

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:

ENSG00000301612 (HGNC:):

ENSG00000301612 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32828844).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006477.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASL10A	NM_006477.5	MANE Select	c.329G>A	p.Arg110His	missense	Exon 2 of 3	NP_006468.1	Q92737-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RASL10A	ENST00000216101.7	TSL:1 MANE Select	c.329G>A	p.Arg110His	missense	Exon 2 of 3	ENSP00000216101.6	Q92737-1
RASL10A	ENST00000942940.1		c.326G>A	p.Arg109His	missense	Exon 2 of 3	ENSP00000612999.1
RASL10A	ENST00000942941.1		c.296G>A	p.Arg99His	missense	Exon 2 of 3	ENSP00000613000.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461264

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726974

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.0000189

AC:

AN:

52824

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111998

Other (OTH)

AF:

0.00

AC:

AN:

60390

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.250

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.022

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.90

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.53

MutationAssessor

Benign

-0.10

PhyloP100

5.7

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.37

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0040

Polyphen

0.99

Vest4

0.19

MutPred

0.57

Gain of ubiquitination at K105 (P = 0.0982)

MVP

0.38

MPC

2.5

ClinPred

0.98

GERP RS

2.8

Varity_R

0.21

gMVP

0.68

Mutation Taster

=75/25

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over