chr19-15451887-C-A

Variant names:

• chr19-15451887-C-A
• NM_022904.3:c.2944G>T

Variant summary

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

The NM_022904.3(RASAL3):​c.2944G>T​(p.Val982Phe) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: RASAL3 NM_022904.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.04
• Publications: 0 publications found

Genes affected

RASAL3 (HGNC:26129): (RAS protein activator like 3) This gene belongs to the Ras GTPase-activating proteins (RasGAP) family and encodes a protein with pleckstrin homology (PH), C2, and Ras GTPase-activation protein (RasGAP) domains. This protein is localized near or at the plasma membrane when expressed exogenously. Reduced expression of this gene in some cell lines resulted in increased levels of the active form of Ras (Ras-GTP), suggesting that this gene may play a role in negatively regulating the Ras signaling pathway. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2017]

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=0.12441808).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022904.3. 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
	RASAL3	NM_022904.3	MANE Select	c.2944G>T	p.Val982Phe	missense	Exon 18 of 18	NP_075055.1	Q86YV0-1
	RASAL3	NM_001400377.1		c.2953G>T	p.Val985Phe	missense	Exon 18 of 18	NP_001387306.1
	RASAL3	NM_001400378.1		c.2926G>T	p.Val976Phe	missense	Exon 18 of 18	NP_001387307.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASAL3	ENST00000343625.12	TSL:2 MANE Select	c.2944G>T	p.Val982Phe	missense	Exon 18 of 18	ENSP00000341905.5	Q86YV0-1
	RASAL3	ENST00000909962.1		c.2971G>T	p.Val991Phe	missense	Exon 18 of 18	ENSP00000580021.1
	RASAL3	ENST00000909960.1		c.2953G>T	p.Val985Phe	missense	Exon 18 of 18	ENSP00000580019.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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	0.10
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	6.7
DANN	Uncertain	0.98
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.9	L
PhyloP100		-2.0
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.28
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.012	D
Polyphen		0.58	P
Vest4		0.29
MutPred		0.20		Loss of MoRF binding (P = 0.0847)
MVP		0.30
MPC		0.025
ClinPred		0.42	T
GERP RS		-4.8
Varity_R		0.11
gMVP		0.29
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: chr19-15562698;