rs1275578970

Variant names:

• chr22-29313437-C-G
• NM_006477.5:c.476G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-29313437-C-G
• chr22-29313437-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006477.5(RASL10A):​c.476G>C​(p.Cys159Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000072 in 1,388,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C159Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: RASL10A NM_006477.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.80

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.872

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASL10A	NM_006477.5	c.476G>C	p.Cys159Ser	missense_variant	Exon 3 of 3	ENST00000216101.7	NP_006468.1
RASL10A	XM_011529822.1	c.536G>C	p.Cys179Ser	missense_variant	Exon 4 of 4		XP_011528124.1
RASL10A	XM_011529823.2	c.332G>C	p.Cys111Ser	missense_variant	Exon 3 of 3		XP_011528125.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASL10A	ENST00000216101.7	c.476G>C	p.Cys159Ser	missense_variant	Exon 3 of 3	1	NM_006477.5	ENSP00000216101.6
RASL10A	ENST00000401450	c.*422G>C		3_prime_UTR_variant	Exon 2 of 2	2		ENSP00000386095.3
RASL10A	ENST00000474590.1	n.*98G>C		downstream_gene_variant		2
RASL10A	ENST00000608559.1	n.*66G>C		downstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.20e-7 AC: 1 AN: 1388784 Hom.: 0 Cov.: 31 AF XY: 0.00000146 AC XY: 1 AN XY: 685698

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: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.24	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	0.068	D
MutationAssessor	Uncertain	2.1	M
PrimateAI	Pathogenic	0.97	D
PROVEAN	Pathogenic	-8.0	D
REVEL	Pathogenic	0.70
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.020	D
Polyphen		0.98	D
Vest4		0.78
MutPred		0.66		Gain of MoRF binding (P = 0.2124);
MVP		0.62
MPC		2.6
ClinPred		1.0	D
GERP RS		4.2
Varity_R		0.96
gMVP		0.87

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: chr22-29709426;