15-65058608-T-C

Variant names:

• chr15-65058608-T-C
• NM_016563.4:c.244A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016563.4(RASL12):​c.244A>G​(p.Arg82Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,408,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: RASL12 NM_016563.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.20

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36690688).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASL12	NM_016563.4	c.244A>G	p.Arg82Gly	missense_variant	Exon 4 of 5	ENST00000220062.9	NP_057647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASL12	ENST00000220062.9	c.244A>G	p.Arg82Gly	missense_variant	Exon 4 of 5	1	NM_016563.4	ENSP00000220062.4
RASL12	ENST00000434605.2	c.211A>G	p.Arg71Gly	missense_variant	Exon 4 of 5	2		ENSP00000412787.2
RASL12	ENST00000421977.7	c.187A>G	p.Arg63Gly	missense_variant	Exon 3 of 4	2		ENSP00000390028.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1408294 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 694938

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000264

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.244A>G (p.R82G) alteration is located in exon 4 (coding exon 4) of the RASL12 gene. This alteration results from a A to G substitution at nucleotide position 244, causing the arginine (R) at amino acid position 82 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T;.;.
Eigen	Benign	-0.069
Eigen_PC	Benign	0.0073
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.6	L;.;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Uncertain	0.51
Sift	Benign	0.16	T;T;T
Sift4G	Benign	0.38	T;T;T
Polyphen		0.73	P;.;.
Vest4		0.29
MutPred		0.67		Loss of phosphorylation at T80 (P = 0.0981);.;.;
MVP		0.82
MPC		0.29
ClinPred		0.31	T
GERP RS		3.0
Varity_R		0.32
gMVP		0.57

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: chr15-65350946;