rs755504855

Variant names:

• chr19-15451913-C-G
• rs755504855
• NM_022904.3:c.2918G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-15451913-C-G
• chr19-15451913-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_022904.3(RASAL3):​c.2918G>C​(p.Arg973Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,607,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: RASAL3 NM_022904.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.93
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.022850484).

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.2918G>C	p.Arg973Thr	missense	Exon 18 of 18	NP_075055.1	Q86YV0-1
	RASAL3	NM_001400377.1		c.2927G>C	p.Arg976Thr	missense	Exon 18 of 18	NP_001387306.1
	RASAL3	NM_001400378.1		c.2900G>C	p.Arg967Thr	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.2918G>C	p.Arg973Thr	missense	Exon 18 of 18	ENSP00000341905.5	Q86YV0-1
	RASAL3	ENST00000909962.1		c.2945G>C	p.Arg982Thr	missense	Exon 18 of 18	ENSP00000580021.1
	RASAL3	ENST00000909960.1		c.2927G>C	p.Arg976Thr	missense	Exon 18 of 18	ENSP00000580019.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152202 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000202 AC: 5 AN: 248066 AF XY: 0.0000297

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000165 AC: 24 AN: 1455716 Hom.: 0 Cov.: 31 AF XY: 0.0000208 AC XY: 15 AN XY: 722698

African (AFR) AF: 0.00 AC: 0 AN: 33376

American (AMR) AF: 0.00 AC: 0 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39522

South Asian (SAS) AF: 0.000186 AC: 16 AN: 86146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53212

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5750

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1106964

Other (OTH) AF: 0.0000999 AC: 6 AN: 60068

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152202 Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1 AN XY: 74356

African (AFR) AF: 0.0000965 AC: 4 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000248 AC: 3

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	0.083
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	0.18
DANN	Benign	0.66
DEOGEN2	Benign	0.0076	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.90	L
PhyloP100		-1.9
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.16
Sift	Benign	0.26	T
Sift4G	Benign	0.60	T
Polyphen		0.020	B
Vest4		0.080
MutPred		0.15		Loss of MoRF binding (P = 0.0246)
MVP		0.21
MPC		0.0094
ClinPred		0.052	T
GERP RS		-8.2
Varity_R		0.036
gMVP		0.080
Mutation Taster		=100/0	polymorphism

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

dbSNP: rs755504855; hg19: chr19-15562724;