11-65794674-G-A

Position:

• chr11-65794674-G-A

Variant summary

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

The NM_004561.4(OVOL1):​c.455G>A​(p.Gly152Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: OVOL1 NM_004561.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.82

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]

LOC124902693 (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
OVOL1	NM_004561.4	c.455G>A	p.Gly152Glu	missense_variant	3/4	ENST00000335987.8	NP_004552.2
LOC124902693	XM_047427980.1	c.*1162-2287C>T		intron_variant			XP_047283936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OVOL1	ENST00000335987.8	c.455G>A	p.Gly152Glu	missense_variant	3/4	1	NM_004561.4	ENSP00000337862.3
OVOL1	ENST00000532448.1	c.269G>A	p.Gly90Glu	missense_variant	2/3	1		ENSP00000434220.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.455G>A (p.G152E) alteration is located in exon 3 (coding exon 3) of the OVOL1 gene. This alteration results from a G to A substitution at nucleotide position 455, causing the glycine (G) at amino acid position 152 to be replaced by a glutamic acid (E). 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	0.90
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.66	D;.
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-7.6	D;D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		1.0	D;.
Vest4		0.68
MutPred		0.58		Loss of MoRF binding (P = 0.0797);.;
MVP		0.62
MPC		1.7
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.82
gMVP		0.64

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

Other links and lift over

dbSNP: rs1858093215; hg19: chr11-65562145;