Variant 11-65795215-G-T 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_004561.4(OVOL1):c.678G>T(p.Glu226Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,354 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 1 hom. )

Consequence

OVOL1
NM_004561.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.855

Variant links:

Genes affected

OVOL1 (HGNC:8525): (ovo like transcriptional repressor 1) This gene encodes a putative zinc finger containing transcription factor that is highly similar to homologous protein in Drosophila and mouse. Based on known functions in these species, this protein is likely involved in hair formation and spermatogenesis in human as well. [provided by RefSeq, Aug 2011]

OVOL1 links:

LOC124902693 (HGNC:):

LOC124902693 links:

Genome browser will be placed here

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=0.12771451).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OVOL1	NM_004561.4 link	c.678G>T	p.Glu226Asp	missense_variant	4/4	ENST00000335987.8	NP_004552.2	O14753
LOC124902693	XM_047427980.1 link	c.*1162-2828C>A		intron_variant			XP_047283936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OVOL1	ENST00000335987.8 link	c.678G>T	p.Glu226Asp	missense_variant	4/4	1	NM_004561.4	ENSP00000337862.3		O14753
OVOL1	ENST00000532448.1 link	c.492G>T	p.Glu164Asp	missense_variant	3/3	1		ENSP00000434220.1		G3V1B0

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000478

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461198

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

726900

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:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.000478

Bravo

AF:

0.0000113

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

Jul 25, 2024

The c.678G>T (p.E226D) alteration is located in exon 4 (coding exon 4) of the OVOL1 gene. This alteration results from a G to T substitution at nucleotide position 678, causing the glutamic acid (E) at amino acid position 226 to be replaced by an aspartic acid (D). 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

Uncertain

0.41

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.48

T;.

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.61

T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.5

D;D

REVEL

Benign

0.14

Sift

Benign

0.19

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.0010

B;.

Vest4

0.062

MVP

0.48

MPC

0.63

ClinPred

0.61

GERP RS

3.3

Varity_R

0.29

gMVP

0.26

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