NM_016563.4:c.603G>C

Variant names:

• chr15-65055097-C-G
• NM_016563.4:c.603G>C

Variant summary

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

The NM_016563.4(RASL12):​c.603G>C​(p.Glu201Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,216 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E201G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RASL12 NM_016563.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.574
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07204321).

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.603G>C	p.Glu201Asp	missense	Exon 5 of 5	NP_057647.1	Q9NYN1-1
	RASL12	NM_001379429.1		c.570G>C	p.Glu190Asp	missense	Exon 5 of 5	NP_001366358.1	Q9NYN1-2
	RASL12	NM_001307930.2		c.546G>C	p.Glu182Asp	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.603G>C	p.Glu201Asp	missense	Exon 5 of 5	ENSP00000220062.4	Q9NYN1-1
	RASL12	ENST00000434605.2	TSL:2	c.570G>C	p.Glu190Asp	missense	Exon 5 of 5	ENSP00000412787.2	Q9NYN1-2
	RASL12	ENST00000421977.7	TSL:2	c.546G>C	p.Glu182Asp	missense	Exon 4 of 4	ENSP00000390028.3	Q9NYN1-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459216 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 725792

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44440

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26044

East Asian (EAS) AF: 0.00 AC: 0 AN: 39618

South Asian (SAS) AF: 0.00 AC: 0 AN: 85832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111060

Other (OTH) AF: 0.00 AC: 0 AN: 60260

GnomAD4 genome Cov.: 32

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	0.076
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.1
DANN	Uncertain	0.99
DEOGEN2	Benign	0.091	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.57
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.12
Sift	Benign	0.46	T
Sift4G	Benign	0.44	T
Polyphen		0.0	B
Vest4		0.050
MutPred		0.24		Gain of helix (P = 0.062)
MVP		0.62
MPC		0.20
ClinPred		0.23	T
GERP RS		0.39
Varity_R		0.051
gMVP		0.098

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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

hg19: chr15-65347435;