20-25075807-TC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014588.6(VSX1):c.*453del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0663 in 166,632 control chromosomes in the GnomAD database, including 1,279 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.072 (1278 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (1 hom.)
• Consequence: VSX1 NM_014588.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.213

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 20-25075807-TC-T is Benign according to our data. Variant chr20-25075807-TC-T is described in ClinVar as [Benign]. Clinvar id is 337949.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VSX1	NM_014588.6	c.*453del		3_prime_UTR_variant	5/5	ENST00000376709.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VSX1	ENST00000376709.9	c.*453del		3_prime_UTR_variant	5/5	1	NM_014588.6	P1

Frequencies

GnomAD3 genomes AF: 0.0719 AC: 10944 AN: 152132 Hom.: 1266 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0276

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.0550

GnomAD4 exome AF: 0.00410 AC: 59 AN: 14382 Hom.: 1 Cov.: 0 AF XY: 0.00430 AC XY: 32 AN XY: 7444

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.0158

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000616

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00762

GnomAD4 genome AF: 0.0722 AC: 10993 AN: 152250 Hom.: 1278 Cov.: 32 AF XY: 0.0690 AC XY: 5141 AN XY: 74456

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.0275

Gnomad4 ASJ AF: 0.00433

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000691

Gnomad4 OTH AF: 0.0544

Alfa AF: 0.00267 Hom.: 5

Bravo AF: 0.0836

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Polymorphous corneal dystrophy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs11478193; hg19: chr20-25056443;