rs1420558322

Variant names:

• chr22-29313450-C-G
• rs1420558322
• NM_006477.5:c.463G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-29313450-C-G
• chr22-29313450-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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]

ENSG00000301612 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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.463G>C	p.Gly155Arg	missense	Exon 3 of 3	NP_006468.1	Q92737-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASL10A	ENST00000216101.7	TSL:1 MANE Select	c.463G>C	p.Gly155Arg	missense	Exon 3 of 3	ENSP00000216101.6	Q92737-1
	RASL10A	ENST00000942940.1		c.460G>C	p.Gly154Arg	missense	Exon 3 of 3	ENSP00000612999.1
	RASL10A	ENST00000942941.1		c.430G>C	p.Gly144Arg	missense	Exon 3 of 3	ENSP00000613000.1

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

African (AFR) AF: 0.00 AC: 0 AN: 31680

American (AMR) AF: 0.00 AC: 0 AN: 35998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25172

East Asian (EAS) AF: 0.00 AC: 0 AN: 35854

South Asian (SAS) AF: 0.00 AC: 0 AN: 79530

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5354

European-Non Finnish (NFE) AF: 0.0000268 AC: 29 AN: 1080614

Other (OTH) AF: 0.00 AC: 0 AN: 57936

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		5.8
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
Mutation Taster		=37/63	disease causing

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

Other links and lift over

dbSNP: rs1420558322; hg19: chr22-29709439;