rs553620483

Variant names:

• chr15-65054973-C-G
• NM_016563.4:c.727G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-65054973-C-G
• chr15-65054973-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016563.4(RASL12):​c.727G>C​(p.Val243Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V243M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RASL12 NM_016563.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.13

Genes affected

RASL12 (HGNC:30289): (RAS like family 12) Predicted to enable GDP binding activity; GTP binding activity; and GTPase activity. Predicted to be involved in signal transduction. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASL12	NM_016563.4	c.727G>C	p.Val243Leu	missense_variant	Exon 5 of 5	ENST00000220062.9	NP_057647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASL12	ENST00000220062.9	c.727G>C	p.Val243Leu	missense_variant	Exon 5 of 5	1	NM_016563.4	ENSP00000220062.4
RASL12	ENST00000434605.2	c.694G>C	p.Val232Leu	missense_variant	Exon 5 of 5	2		ENSP00000412787.2
RASL12	ENST00000421977.7	c.670G>C	p.Val224Leu	missense_variant	Exon 4 of 4	2		ENSP00000390028.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461808 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 727204

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

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	0.85
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.62	D;D;D
MetaSVM	Uncertain	0.14	D
MutationAssessor	Benign	1.0	L;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.88	N;N;N
REVEL	Benign	0.25
Sift	Uncertain	0.013	D;D;D
Sift4G	Pathogenic	0.0	D;D;T
Polyphen		1.0	D;.;.
Vest4		0.60
MutPred		0.19		Loss of catalytic residue at V243 (P = 0.0308);.;.;
MVP		0.90
MPC		0.81
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.35
gMVP		0.39

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: chr15-65347311;