Variant chr2-63056069-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014562.4(OTX1):c.818C>G(p.Ala273Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000197 in 152,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Consequence

OTX1
NM_014562.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.97

Variant links:

Genes affected

OTX1 (HGNC:8521): (orthodenticle homeobox 1) This gene encodes a member of the bicoid sub-family of homeodomain-containing transcription factors. The encoded protein acts as a transcription factor and may play a role in brain and sensory organ development. A similar protein in mouse is required for proper brain and sensory organ development and can cause epilepsy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

OTX1 links:

OTX1 (HGNC:):

OTX1 links:

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ACMG classification

Classification made for transcript

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=0.14628974).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTX1	NM_014562.4 linkuse as main transcript	c.818C>G	p.Ala273Gly	missense_variant	5/5	ENST00000282549.7	NP_055377.1	P32242
OTX1	NM_001199770.2 linkuse as main transcript	c.818C>G	p.Ala273Gly	missense_variant	5/5		NP_001186699.1	P32242
OTX1	NR_130153.2 linkuse as main transcript	n.1181C>G		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OTX1	ENST00000282549.7 linkuse as main transcript	c.818C>G	p.Ala273Gly	missense_variant	5/5	1	NM_014562.4	ENSP00000282549.2	P32242
OTX1	ENST00000366671.7 linkuse as main transcript	c.818C>G	p.Ala273Gly	missense_variant	5/5	3		ENSP00000355631.3	P32242
OTX1	ENST00000405984.8 linkuse as main transcript	n.*627C>G		non_coding_transcript_exon_variant	5/5	2		ENSP00000385782.4	B5MC54
OTX1	ENST00000405984.8 linkuse as main transcript	n.*627C>G		3_prime_UTR_variant	5/5	2		ENSP00000385782.4	B5MC54

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152082

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2024

The c.818C>G (p.A273G) alteration is located in exon 5 (coding exon 3) of the OTX1 gene. This alteration results from a C to G substitution at nucleotide position 818, causing the alanine (A) at amino acid position 273 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.36

T;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.19

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

.;D

M_CAP

Benign

0.066

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-0.64

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

0.35

N;N

REVEL

Benign

0.26

Sift

Benign

1.0

T;T

Sift4G

Benign

0.78

T;T

Polyphen

0.089

B;B

Vest4

0.12

MutPred

0.54

Loss of stability (P = 0.0469);Loss of stability (P = 0.0469);

MVP

0.80

ClinPred

0.43

GERP RS

3.6

Varity_R

0.099

gMVP

0.28

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over