20-25082079-C-T

Variant names:

• chr20-25082079-C-T
• rs8123716
• NM_014588.6:c.18G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014588.6(VSX1):​c.18G>A​(p.Ser6Ser) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S6S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VSX1 NM_014588.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 0 publications found

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]

VSX1 Gene-Disease associations (from GenCC):

• posterior polymorphous corneal dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• keratoconus 1

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: G2P, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• craniofacial anomalies and anterior segment dysgenesis syndrome

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• posterior polymorphous corneal dystrophy 1

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014588.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSX1	NM_014588.6	MANE Select	c.18G>A	p.Ser6Ser	synonymous	Exon 1 of 5	NP_055403.2
	VSX1	NM_001256272.2		c.18G>A	p.Ser6Ser	synonymous	Exon 1 of 5	NP_001243201.1
	VSX1	NM_199425.3		c.18G>A	p.Ser6Ser	synonymous	Exon 1 of 3	NP_955457.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSX1	ENST00000376709.9	TSL:1 MANE Select	c.18G>A	p.Ser6Ser	synonymous	Exon 1 of 5	ENSP00000365899.3
	VSX1	ENST00000429762.7	TSL:1	c.18G>A	p.Ser6Ser	synonymous	Exon 1 of 5	ENSP00000401690.3
	VSX1	ENST00000376707.4	TSL:1	c.18G>A	p.Ser6Ser	synonymous	Exon 1 of 3	ENSP00000365897.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1386150 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 684294

African (AFR) AF: 0.00 AC: 0 AN: 31984

American (AMR) AF: 0.00 AC: 0 AN: 35884

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25166

East Asian (EAS) AF: 0.00 AC: 0 AN: 36334

South Asian (SAS) AF: 0.00 AC: 0 AN: 79484

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5386

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080300

Other (OTH) AF: 0.00 AC: 0 AN: 57990

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	6.2
DANN	Benign	0.92
PhyloP100		-0.037
PromoterAI		-0.099	Neutral

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: rs8123716; hg19: chr20-25062715;