22-29313870-C-G

Position:

• chr22-29313870-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006477.5(RASL10A):​c.337G>C​(p.Glu113Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 33)
• Consequence: RASL10A NM_006477.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.44

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39181077).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASL10A	NM_006477.5	c.337G>C	p.Glu113Gln	missense_variant	2/3	ENST00000216101.7	NP_006468.1
RASL10A	XM_011529822.1	c.397G>C	p.Glu133Gln	missense_variant	3/4		XP_011528124.1
RASL10A	XM_011529823.2	c.193G>C	p.Glu65Gln	missense_variant	2/3		XP_011528125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASL10A	ENST00000216101.7	c.337G>C	p.Glu113Gln	missense_variant	2/3	1	NM_006477.5	ENSP00000216101.6
RASL10A	ENST00000401450.3	c.337G>C	p.Glu113Gln	missense_variant	2/2	2		ENSP00000386095.3
RASL10A	ENST00000474590.1	n.203G>C		non_coding_transcript_exon_variant	2/2	2
RASL10A	ENST00000608559.1	n.489G>C		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Jul 27, 2024

The c.337G>C (p.E113Q) alteration is located in exon 2 (coding exon 2) of the RASL10A gene. This alteration results from a G to C substitution at nucleotide position 337, causing the glutamic acid (E) at amino acid position 113 to be replaced by a glutamine (Q). 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	0.15
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	.;D
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.64	T;D
M_CAP	Benign	0.084	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-2.2	N;N
REVEL	Uncertain	0.31
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.034	D;D
Polyphen		0.94	.;P
Vest4		0.31
MutPred		0.43		Gain of glycosylation at P116 (P = 0.1717);Gain of glycosylation at P116 (P = 0.1717);
MVP		0.65
MPC		2.4
ClinPred		0.98	D
GERP RS		3.9
Varity_R		0.35
gMVP		0.61

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.

Other links and lift over

hg19: chr22-29709859;