Variant 5-77636984-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_032109.3(OTP):c.284C>T(p.Ala95Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00505 in 1,613,904 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0039 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0052 ( 36 hom. )

Consequence

OTP
NM_032109.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.50

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0064309537).

BP6

Variant 5-77636984-G-A is Benign according to our data. Variant chr5-77636984-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2655552.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 601 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTP	NM_032109.3 linkuse as main transcript	c.284C>T	p.Ala95Val	missense_variant	2/3	ENST00000306422.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTP	ENST00000306422.5 linkuse as main transcript	c.284C>T	p.Ala95Val	missense_variant	2/3	1	NM_032109.3	P1
OTP	ENST00000515716.1 linkuse as main transcript	n.10C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00394

AC:

600

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00405

Gnomad ASJ

AF:

0.0222

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00551

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00553

AC:

1379

AN:

249372

Hom.:

AF XY:

0.00591

AC XY:

798

AN XY:

134994

show subpopulations

Gnomad AFR exome

AF:

0.000741

Gnomad AMR exome

AF:

0.00359

Gnomad ASJ exome

AF:

0.0249

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00640

Gnomad FIN exome

AF:

0.000930

Gnomad NFE exome

AF:

0.00650

Gnomad OTH exome

AF:

0.00800

GnomAD4 exome

AF:

0.00516

AC:

7545

AN:

1461576

Hom.:

Cov.:

AF XY:

0.00536

AC XY:

3894

AN XY:

727102

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.00409

Gnomad4 ASJ exome

AF:

0.0229

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00671

Gnomad4 FIN exome

AF:

0.000695

Gnomad4 NFE exome

AF:

0.00511

Gnomad4 OTH exome

AF:

0.00585

GnomAD4 genome

AF:

0.00395

AC:

601

AN:

152328

Hom.:

Cov.:

AF XY:

0.00371

AC XY:

276

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00115

Gnomad4 AMR

AF:

0.00405

Gnomad4 ASJ

AF:

0.0222

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.00551

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.0193

Hom.:

727

Bravo

AF:

0.00414

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00570

AC:

ExAC

AF:

0.00563

AC:

683

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00818

EpiControl

AF:

0.00984

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

OTP: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.083

Eigen

Benign

-0.19

Eigen_PC

Benign

0.015

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.71

M_CAP

Benign

0.041

MetaRNN

Benign

0.0064

MetaSVM

Benign

-0.29

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.87

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.89

REVEL

Benign

0.19

Sift

Benign

0.044

Sift4G

Benign

0.27

Polyphen

0.16

Vest4

0.26

MVP

0.45

MPC

0.86

ClinPred

0.016

GERP RS

4.5

Varity_R

0.18

gMVP

0.27

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