15-65067780-A-T

Position:

• chr15-65067780-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016563.4(RASL12):​c.56T>A​(p.Leu19His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000028 in 1,430,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: RASL12 NM_016563.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.51

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21632409).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASL12	NM_016563.4	c.56T>A	p.Leu19His	missense_variant	1/5	ENST00000220062.9	NP_057647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASL12	ENST00000220062.9	c.56T>A	p.Leu19His	missense_variant	1/5	1	NM_016563.4	ENSP00000220062.4
RASL12	ENST00000421977.7	c.56T>A	p.Leu19His	missense_variant	1/4	2		ENSP00000390028.3
RASL12	ENST00000434605.2	c.71-2507T>A		intron_variant		2		ENSP00000412787.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000280 AC: 4 AN: 1430666 Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1 AN XY: 710258

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: 0.00000364

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2022

The c.56T>A (p.L19H) alteration is located in exon 1 (coding exon 1) of the RASL12 gene. This alteration results from a T to A substitution at nucleotide position 56, causing the leucine (L) at amino acid position 19 to be replaced by a histidine (H). 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	0.16
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Benign	0.95
DEOGEN2	Benign	0.074	T;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.56	T;T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.050	N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.45	N;N
REVEL	Benign	0.18
Sift	Benign	0.21	T;T
Sift4G	Benign	0.40	T;D
Polyphen		0.18	B;.
Vest4		0.25
MutPred		0.37		Gain of disorder (P = 0.0546);Gain of disorder (P = 0.0546);
MVP		0.68
MPC		0.29
ClinPred		0.51	D
GERP RS		2.0
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-65360118;