rs6138482

Variant names:

• chr20-25078806-C-A
• rs6138482
• ENST00000376707.4:c.650G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-25078806-C-A
• chr20-25078806-C-G
• chr20-25078806-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_199425.3(VSX1):​c.650G>T​(p.Arg217Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R217H) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: VSX1 NM_199425.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159

Genes affected

VSX1 (HGNC:12723): (visual system homeobox 1) The protein encoded by this gene contains a paired-like homeodomain and binds to the core of the locus control region of the red/green visual pigment gene cluster. The encoded protein may regulate expression of the cone opsin genes early in development. Mutations in this gene can cause posterior polymorphous corneal dystrophy and keratoconus. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.068140596).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSX1	NM_014588.6	c.627+23G>T		intron_variant	Intron 3 of 4	ENST00000376709.9	NP_055403.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VSX1	ENST00000376709.9	c.627+23G>T		intron_variant	Intron 3 of 4	1	NM_014588.6	ENSP00000365899.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461890 Hom.: 0 Cov.: 71 AF XY: 0.00000413 AC XY: 3 AN XY: 727244

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	1.0
DANN	Benign	0.82
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0022	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.51	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.24
Sift	Benign	0.24	T
Polyphen		0.0	B
Vest4		0.070
MutPred		0.61		Loss of helix (P = 0.0376);
MVP		0.32
ClinPred		0.061	T
GERP RS		-4.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6138482; hg19: chr20-25059442;