15-65067795-G-A

Variant names:

• chr15-65067795-G-A
• NM_016563.4:c.41C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016563.4(RASL12):​c.41C>T​(p.Pro14Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RASL12 NM_016563.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.329
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06658292).

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.41C>T	p.Pro14Leu	missense	Exon 1 of 5	NP_057647.1	Q9NYN1-1
	RASL12	NM_001307930.2		c.41C>T	p.Pro14Leu	missense	Exon 1 of 4	NP_001294859.1	Q9NYN1-3
	RASL12	NM_001379429.1		c.71-2522C>T		intron	N/A	NP_001366358.1	Q9NYN1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASL12	ENST00000220062.9	TSL:1 MANE Select	c.41C>T	p.Pro14Leu	missense	Exon 1 of 5	ENSP00000220062.4	Q9NYN1-1
	RASL12	ENST00000421977.7	TSL:2	c.41C>T	p.Pro14Leu	missense	Exon 1 of 4	ENSP00000390028.3	Q9NYN1-3
	RASL12	ENST00000434605.2	TSL:2	c.71-2522C>T		intron	N/A	ENSP00000412787.2	Q9NYN1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	0.073
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.099	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.33
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.062
Sift	Uncertain	0.023	D
Sift4G	Benign	0.40	T
Polyphen		0.012	B
Vest4		0.045
MutPred		0.20		Loss of disorder (P = 0.0384)
MVP		0.43
MPC		0.23
ClinPred		0.029	T
GERP RS		1.2
PromoterAI		-0.094	Neutral
Varity_R		0.030
gMVP		0.36

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

hg19: chr15-65360133;