15-65067813-G-A

Variant names:

• chr15-65067813-G-A
• rs1242790207
• NM_016563.4:c.23C>T

Variant summary

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

The NM_016563.4(RASL12):​c.23C>T​(p.Pro8Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000703 in 1,422,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: RASL12 NM_016563.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.51

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=0.31140286).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASL12	NM_016563.4	c.23C>T	p.Pro8Leu	missense_variant	Exon 1 of 5	ENST00000220062.9	NP_057647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASL12	ENST00000220062.9	c.23C>T	p.Pro8Leu	missense_variant	Exon 1 of 5	1	NM_016563.4	ENSP00000220062.4
RASL12	ENST00000421977.7	c.23C>T	p.Pro8Leu	missense_variant	Exon 1 of 4	2		ENSP00000390028.3
RASL12	ENST00000434605.2	c.71-2540C>T		intron_variant	Intron 1 of 4	2		ENSP00000412787.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1422268 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 705834

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: 9.12e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.23C>T (p.P8L) alteration is located in exon 1 (coding exon 1) of the RASL12 gene. This alteration results from a C to T substitution at nucleotide position 23, causing the proline (P) at amino acid position 8 to be replaced by a leucine (L). 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	0.15
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T;.
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T;T
M_CAP	Pathogenic	0.42	D
MetaRNN	Benign	0.31	T;T
MetaSVM	Uncertain	-0.038	T
MutationAssessor	Benign	1.6	L;L
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.27
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.016	D;D
Polyphen		0.24	B;.
Vest4		0.35
MutPred		0.33		Gain of MoRF binding (P = 0.0289);Gain of MoRF binding (P = 0.0289);
MVP		0.88
MPC		0.25
ClinPred		0.43	T
GERP RS		4.5
Varity_R		0.23
gMVP		0.48

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

LitVar

Other links and lift over

dbSNP: rs1242790207; hg19: chr15-65360151;