NM_006477.5:c.370A>G

Variant names:

• chr22-29313543-T-C
• rs1446373254
• NM_006477.5:c.370A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006477.5(RASL10A):​c.370A>G​(p.Ile124Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000322 in 1,550,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RASL10A NM_006477.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.42
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29687724).

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.370A>G	p.Ile124Val	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.370A>G	p.Ile124Val	missense	Exon 3 of 3	ENSP00000216101.6	Q92737-1
	RASL10A	ENST00000942940.1		c.367A>G	p.Ile123Val	missense	Exon 3 of 3	ENSP00000612999.1
	RASL10A	ENST00000942941.1		c.337A>G	p.Ile113Val	missense	Exon 3 of 3	ENSP00000613000.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152214 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000118 AC: 2 AN: 169814 AF XY: 0.0000105

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000391

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000688

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1398604 Hom.: 0 Cov.: 31 AF XY: 0.00000289 AC XY: 2 AN XY: 692676

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

African (AFR) AF: 0.00 AC: 0 AN: 31608

American (AMR) AF: 0.0000274 AC: 1 AN: 36502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23602

East Asian (EAS) AF: 0.0000525 AC: 2 AN: 38126

South Asian (SAS) AF: 0.00 AC: 0 AN: 79568

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36102

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4098

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1091062

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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0225104), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152214 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74366

African (AFR) AF: 0.00 AC: 0 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Benign	0.17
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	0.40	N
PhyloP100		7.4
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.52	N
REVEL	Uncertain	0.40
Sift	Benign	0.28	T
Sift4G	Benign	0.33	T
Polyphen		0.25	B
Vest4		0.48
MutPred		0.56		Gain of disorder (P = 0.0756)
MVP		0.37
MPC		1.1
ClinPred		0.40	T
GERP RS		4.8
Varity_R		0.13
gMVP		0.49
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1446373254; hg19: chr22-29709532;