Variant 5-77630477-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_032109.3(OTP):c.765C>A(p.Ser255Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,592,330 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

OTP
NM_032109.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.03

Variant links:

Genes affected

OTP (HGNC:8518): (orthopedia homeobox) This gene encodes a member of the homeodomain (HD) family. HD family proteins are helix-turn-helix transcription factors that play key roles in the specification of cell fates. This protein may function during brain development. [provided by RefSeq, Jul 2008]

OTP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTP	NM_032109.3 link	c.765C>A	p.Ser255Arg	missense_variant	3/3	ENST00000306422.5	NP_115485.1	Q5XKR4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTP	ENST00000306422.5 link	c.765C>A	p.Ser255Arg	missense_variant	3/3	1	NM_032109.3	ENSP00000302814.3		Q5XKR4

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

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:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000744

AC:

AN:

201672

Hom.:

AF XY:

0.0000721

AC XY:

AN XY:

110904

show subpopulations

Gnomad AFR exome

AF:

0.0000922

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000162

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000210

AC:

302

AN:

1440142

Hom.:

Cov.:

AF XY:

0.000192

AC XY:

137

AN XY:

714696

show subpopulations

Gnomad4 AFR exome

AF:

0.000122

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:

0.000255

Gnomad4 OTH exome

AF:

0.000286

GnomAD4 genome

AF:

0.000145

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0000965

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:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000271

Hom.:

Bravo

AF:

0.000178

ExAC

AF:

0.0000672

AC:

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

Jan 24, 2023

The c.765C>A (p.S255R) alteration is located in exon 3 (coding exon 3) of the OTP gene. This alteration results from a C to A substitution at nucleotide position 765, causing the serine (S) at amino acid position 255 to be replaced by an arginine (R). 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

Pathogenic

0.85

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.19

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.66

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.96

MetaRNN

Uncertain

0.53

MetaSVM

Benign

-0.52

MutationAssessor

Benign

1.6

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.53

Sift

Benign

0.34

Sift4G

Benign

0.56

Polyphen

0.58

Vest4

0.59

MutPred

0.34

Loss of glycosylation at S255 (P = 0.028);

MVP

0.83

MPC

0.98

ClinPred

0.058

GERP RS

2.7

Varity_R

0.24

gMVP

0.66

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