NM_016563.4:c.727G>C

Variant names:

• chr15-65054973-C-G
• rs553620483
• NM_016563.4:c.727G>C

Variant summary

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

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

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_016563.4. 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
	RASL12	NM_016563.4	MANE Select	c.727G>C	p.Val243Leu	missense	Exon 5 of 5	NP_057647.1	Q9NYN1-1
	RASL12	NM_001379429.1		c.694G>C	p.Val232Leu	missense	Exon 5 of 5	NP_001366358.1	Q9NYN1-2
	RASL12	NM_001307930.2		c.670G>C	p.Val224Leu	missense	Exon 4 of 4	NP_001294859.1	Q9NYN1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASL12	ENST00000220062.9	TSL:1 MANE Select	c.727G>C	p.Val243Leu	missense	Exon 5 of 5	ENSP00000220062.4	Q9NYN1-1
	RASL12	ENST00000434605.2	TSL:2	c.694G>C	p.Val232Leu	missense	Exon 5 of 5	ENSP00000412787.2	Q9NYN1-2
	RASL12	ENST00000421977.7	TSL:2	c.670G>C	p.Val224Leu	missense	Exon 4 of 4	ENSP00000390028.3	Q9NYN1-3

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

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111988

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Uncertain	0.14	D
MutationAssessor	Benign	1.0	L
PhyloP100		7.1
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.25
Sift	Uncertain	0.013	D
Sift4G	Pathogenic	0.0	D
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

Other links and lift over

dbSNP: rs553620483; hg19: chr15-65347311;