1-107964707-T-C

Variant names:

• chr1-107964707-T-C
• rs2101432623
• NM_006113.5:c.163A>G

Variant summary

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

The NM_006113.5(VAV3):​c.163A>G​(p.Ile55Val) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I55M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VAV3 NM_006113.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.49
• Publications: 0 publications found

Genes affected

VAV3 (HGNC:12659): (vav guanine nucleotide exchange factor 3) This gene is a member of the VAV gene family. The VAV proteins are guanine nucleotide exchange factors (GEFs) for Rho family GTPases that activate pathways leading to actin cytoskeletal rearrangements and transcriptional alterations. This gene product acts as a GEF preferentially for RhoG, RhoA, and to a lesser extent, RAC1, and it associates maximally with the nucleotide-free states of these GTPases. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

VAV3-AS1 (HGNC:40608): (VAV3 antisense RNA 1)

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=0.18871677).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006113.5. 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
	VAV3	NM_006113.5	MANE Select	c.163A>G	p.Ile55Val	missense	Exon 1 of 27	NP_006104.4
	VAV3-AS1	NR_046653.1		n.62+203T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAV3	ENST00000370056.9	TSL:1 MANE Select	c.163A>G	p.Ile55Val	missense	Exon 1 of 27	ENSP00000359073.4	Q9UKW4-1
	VAV3	ENST00000527011.5	TSL:1	c.163A>G	p.Ile55Val	missense	Exon 1 of 28	ENSP00000432540.1	Q9UKW4-4
	VAV3	ENST00000923907.1		c.163A>G	p.Ile55Val	missense	Exon 1 of 28	ENSP00000593966.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	0.088
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.073	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.41	N
PhyloP100		2.5
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.058
Sift	Benign	0.21	T
Sift4G	Benign	0.19	T
Polyphen		0.031	B
Vest4		0.32
MutPred		0.43		Gain of methylation at R51 (P = 0.1201)
MVP		0.70
MPC		0.29
ClinPred		0.53	D
GERP RS		3.8
PromoterAI		0.039	Neutral
Varity_R		0.13
gMVP		0.37
Mutation Taster		=289/11	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: rs2101432623; hg19: chr1-108507329;