22-29313450-C-G

Position:

• chr22-29313450-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006477.5(RASL10A):​c.463G>C​(p.Gly155Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000209 in 1,389,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: RASL10A NM_006477.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.75

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASL10A	NM_006477.5	c.463G>C	p.Gly155Arg	missense_variant	3/3	ENST00000216101.7	NP_006468.1
RASL10A	XM_011529822.1	c.523G>C	p.Gly175Arg	missense_variant	4/4		XP_011528124.1
RASL10A	XM_011529823.2	c.319G>C	p.Gly107Arg	missense_variant	3/3		XP_011528125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASL10A	ENST00000216101.7	c.463G>C	p.Gly155Arg	missense_variant	3/3	1	NM_006477.5	ENSP00000216101.6
RASL10A	ENST00000401450.3	c.*409G>C		3_prime_UTR_variant	2/2	2		ENSP00000386095.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000209 AC: 29 AN: 1389884 Hom.: 0 Cov.: 31 AF XY: 0.0000131 AC XY: 9 AN XY: 686464

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: 0.0000268

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2023

The c.463G>C (p.G155R) alteration is located in exon 3 (coding exon 3) of the RASL10A gene. This alteration results from a G to C substitution at nucleotide position 463, causing the glycine (G) at amino acid position 155 to be replaced by an arginine (R). 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	0.68
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.52	D
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	1.4	L
PrimateAI	Pathogenic	0.95	D
PROVEAN	Pathogenic	-5.3	D
REVEL	Pathogenic	0.70
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.17	T
Polyphen		1.0	D
Vest4		0.41
MutPred		0.52		Gain of MoRF binding (P = 0.1005);
MVP		0.60
MPC		2.6
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.86
gMVP		0.78

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

Other links and lift over

dbSNP: rs1420558322; hg19: chr22-29709439;