rs1664603979

Variant names:

• chr2-17592082-A-G
• rs1664603979
• NM_003385.5:c.8A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003385.5(VSNL1):​c.8A>G​(p.Lys3Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: VSNL1 NM_003385.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.32
• Publications: 0 publications found

Genes affected

VSNL1 (HGNC:12722): (visinin like 1) This gene is a member of the visinin/recoverin subfamily of neuronal calcium sensor proteins. The encoded protein is strongly expressed in granule cells of the cerebellum where it associates with membranes in a calcium-dependent manner and modulates intracellular signaling pathways of the central nervous system by directly or indirectly regulating the activity of adenylyl cyclase. Alternatively spliced transcript variants have been observed, but their full-length nature has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40319398).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003385.5. 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
	VSNL1	NM_003385.5	MANE Select	c.8A>G	p.Lys3Arg	missense	Exon 2 of 4	NP_003376.2
	VSNL1	NM_001366804.2		c.8A>G	p.Lys3Arg	missense	Exon 2 of 5	NP_001353733.1
	VSNL1	NM_001366803.2		c.8A>G	p.Lys3Arg	missense	Exon 2 of 4	NP_001353732.1	P62760

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSNL1	ENST00000295156.9	TSL:1 MANE Select	c.8A>G	p.Lys3Arg	missense	Exon 2 of 4	ENSP00000295156.4	P62760
	VSNL1	ENST00000404666.6	TSL:3	c.8A>G	p.Lys3Arg	missense	Exon 2 of 4	ENSP00000384014.1	P62760
	VSNL1	ENST00000913178.1		c.8A>G	p.Lys3Arg	missense	Exon 2 of 5	ENSP00000583237.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.13
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		9.3
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.28
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.012	D
Polyphen		0.47	P
Vest4		0.49
MutPred		0.21		Loss of ubiquitination at K3 (P = 0.0141)
MVP		0.36
MPC		1.3
ClinPred		0.97	D
GERP RS		5.4
Varity_R		0.30
gMVP		0.78
Mutation Taster		=60/40	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: rs1664603979; hg19: chr2-17773349;