rs368948417

Variant names:

• chr22-29315039-C-G
• rs368948417
• NM_006477.5:c.208G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-29315039-C-G
• chr22-29315039-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006477.5(RASL10A):​c.208G>C​(p.Gly70Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000736 in 1,358,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: RASL10A NM_006477.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18572941).

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.208G>C	p.Gly70Arg	missense	Exon 1 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.208G>C	p.Gly70Arg	missense	Exon 1 of 3	ENSP00000216101.6	Q92737-1
	RASL10A	ENST00000942940.1		c.208G>C	p.Gly70Arg	missense	Exon 1 of 3	ENSP00000612999.1
	RASL10A	ENST00000942941.1		c.208G>C	p.Gly70Arg	missense	Exon 1 of 3	ENSP00000613000.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.36e-7 AC: 1 AN: 1358094 Hom.: 0 Cov.: 31 AF XY: 0.00000149 AC XY: 1 AN XY: 668902

African (AFR) AF: 0.00 AC: 0 AN: 28320

American (AMR) AF: 0.00 AC: 0 AN: 33282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24060

East Asian (EAS) AF: 0.00 AC: 0 AN: 32678

South Asian (SAS) AF: 0.0000131 AC: 1 AN: 76350

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35024

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5582

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1066154

Other (OTH) AF: 0.00 AC: 0 AN: 56644

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	12
DANN	Benign	0.93
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.56	T
M_CAP	Pathogenic	0.48	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	0.46	N
PhyloP100		0.15
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.18
Sift	Benign	0.27	T
Sift4G	Benign	0.24	T
Polyphen		0.41	B
Vest4		0.062
MutPred		0.66		Gain of solvent accessibility (P = 0.006)
MVP		0.14
MPC		2.3
ClinPred		0.13	T
GERP RS		-2.2
Varity_R		0.051
gMVP		0.61
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs368948417; hg19: chr22-29711028;