chr20-25071957-G-A

Position:

• chr20-25071957-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000444511.6(VSX1):​c.689C>T​(p.Pro230Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000404 in 495,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000040 (0 hom.)
• Consequence: VSX1 ENST00000444511.6 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -1.38

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056037635).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSX1	NM_001256271.2	c.689C>T	p.Pro230Leu	missense_variant	4/4		NP_001243200.1
VSX1	NM_001256272.2	c.870C>T	p.Pro290=	synonymous_variant	5/5		NP_001243201.1
VSX1	XM_017027837.2	c.*652C>T		3_prime_UTR_variant	5/5		XP_016883326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSX1	ENST00000444511.6	c.689C>T	p.Pro230Leu	missense_variant	4/4	1		ENSP00000387720
VSX1	ENST00000429762.7	c.870C>T	p.Pro290=	synonymous_variant	5/5	1		ENSP00000401690
VSX1	ENST00000409285.6	c.*135C>T		3_prime_UTR_variant, NMD_transcript_variant	6/6	1		ENSP00000386612
VSX1	ENST00000409958.6	c.*140C>T		3_prime_UTR_variant, NMD_transcript_variant	5/5	1		ENSP00000387069

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000404 AC: 2 AN: 495170 Hom.: 0 Cov.: 0 AF XY: 0.00000763 AC XY: 2 AN XY: 262118

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000706

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	0.41
DANN	Benign	0.73
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0090	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-0.58	T
MutationTaster	Benign	1.0	N;N
PROVEAN	Benign	0.87	N
REVEL	Benign	0.16
Sift	Benign	0.18	T
Polyphen		0.0	B
Vest4		0.060
MutPred		0.29		Gain of MoRF binding (P = 0.0208);
MVP		0.54
ClinPred		0.037	T
GERP RS		-3.8

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-25052593;