5-77630593-C-T

Variant summary

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

The NM_032109.3(OTP):​c.649G>A​(p.Val217Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000071 in 1,408,176 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

OTP
NM_032109.3 missense

Scores

2
9
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.68
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OTPNM_032109.3 linkc.649G>A p.Val217Met missense_variant Exon 3 of 3 ENST00000306422.5 NP_115485.1 Q5XKR4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OTPENST00000306422.5 linkc.649G>A p.Val217Met missense_variant Exon 3 of 3 1 NM_032109.3 ENSP00000302814.3 Q5XKR4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000631
AC:
1
AN:
158416
Hom.:
0
AF XY:
0.0000114
AC XY:
1
AN XY:
87840
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.00
Gnomad OTH exome
AF:
0.000226
GnomAD4 exome
AF:
7.10e-7
AC:
1
AN:
1408176
Hom.:
0
Cov.:
30
AF XY:
0.00000143
AC XY:
1
AN XY:
697046
show subpopulations
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:
0.00
Gnomad4 OTH exome
AF:
0.0000171
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 11, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.649G>A (p.V217M) alteration is located in exon 3 (coding exon 3) of the OTP gene. This alteration results from a G to A substitution at nucleotide position 649, causing the valine (V) at amino acid position 217 to be replaced by a methionine (M). 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
0.18
BayesDel_addAF
Uncertain
0.10
D
BayesDel_noAF
Benign
-0.090
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.057
T
Eigen
Uncertain
0.28
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.90
D
M_CAP
Pathogenic
0.86
D
MetaRNN
Uncertain
0.43
T
MetaSVM
Uncertain
0.47
D
MutationAssessor
Benign
1.5
L
PrimateAI
Pathogenic
0.91
D
PROVEAN
Benign
0.15
N
REVEL
Uncertain
0.34
Sift
Benign
0.15
T
Sift4G
Benign
0.32
T
Polyphen
1.0
D
Vest4
0.33
MutPred
0.22
Gain of disorder (P = 0.0975);
MVP
0.74
MPC
0.92
ClinPred
0.79
D
GERP RS
3.6
Varity_R
0.13
gMVP
0.72

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.

Other links and lift over

dbSNP: rs1214582093; hg19: chr5-76926418; API