rs796052181

chr20-25081787-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4 BP6

The NM_014588.6(VSX1):c.310G>C(p.Ala104Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000074 in 1,351,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: VSX1 NM_014588.6 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.300

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33886945).
• BP6: Variant 20-25081787-C-G is Benign according to our data. Variant chr20-25081787-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 207909.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VSX1	NM_014588.6	c.310G>C	p.Ala104Pro	missense_variant	1/5	ENST00000376709.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VSX1	ENST00000376709.9	c.310G>C	p.Ala104Pro	missense_variant	1/5	1	NM_014588.6	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.40e-7 AC: 1 AN: 1351102 Hom.: 0 Cov.: 31 AF XY: 0.00000150 AC XY: 1 AN XY: 666038

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: 0.0000301

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Long QT syndrome Benign:1

Likely benign, no assertion criteria provided

research

Medical Research Institute, Tokyo Medical and Dental University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.084	D
BayesDel_noAF	Benign	-0.12
Cadd	Benign	10
Dann	Benign	0.97
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.72	T;T;T;T
M_CAP	Pathogenic	0.92	D
MetaRNN	Benign	0.34	T;T;T;T
MetaSVM	Uncertain	0.047	D
MutationAssessor	Uncertain	2.4	M;M;M;M
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Uncertain	0.41
Sift	Uncertain	0.022	D;D;D;D
Sift4G	Uncertain	0.049	D;D;T;D
Polyphen		0.73	P;P;P;P
Vest4		0.31
MutPred		0.28		Loss of stability (P = 0.0382);Loss of stability (P = 0.0382);Loss of stability (P = 0.0382);Loss of stability (P = 0.0382);
MVP		0.80
MPC		0.24
ClinPred		0.40	T
GERP RS		-1.9
Varity_R		0.22
gMVP		0.54

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: rs796052181; hg19: chr20-25062423;