chr11-65794066-G-C

Position:

• chr11-65794066-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004561.4(OVOL1):​c.136G>C​(p.Glu46Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 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: 1.76

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10753974).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OVOL1	NM_004561.4	c.136G>C	p.Glu46Gln	missense_variant	2/4	ENST00000335987.8	NP_004552.2
LOC124902693	XM_047427980.1	c.*1162-1679C>G		intron_variant			XP_047283936.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OVOL1	ENST00000335987.8	c.136G>C	p.Glu46Gln	missense_variant	2/4	1	NM_004561.4	ENSP00000337862.3
OVOL1	ENST00000532448.1	c.-51G>C		5_prime_UTR_variant	1/3	1		ENSP00000434220.1
OVOL1	ENST00000531907.1	n.529G>C		non_coding_transcript_exon_variant	3/3	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

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

Oct 14, 2023

The c.136G>C (p.E46Q) alteration is located in exon 2 (coding exon 2) of the OVOL1 gene. This alteration results from a G to C substitution at nucleotide position 136, causing the glutamic acid (E) at amino acid position 46 to be replaced by a glutamine (Q). 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	0.22
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.060
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.37	N
REVEL	Benign	0.096
Sift	Benign	0.27	T
Sift4G	Benign	0.55	T
Polyphen		0.022	B
Vest4		0.22
MutPred		0.46		Loss of glycosylation at P47 (P = 0.0909);
MVP		0.50
MPC		0.68
ClinPred		0.15	T
GERP RS		5.0
Varity_R		0.14
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-65561537;