Variant X-83508515-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP4

The NM_000307.5(POU3F4):c.191G>A(p.Gly64Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000459 in 1,089,456 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000046 ( 0 hom. 1 hem. )

Consequence

POU3F4
NM_000307.5 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 5.72

Variant links:

Genes affected

POU3F4 (HGNC:9217): (POU class 3 homeobox 4) This gene encodes a member of the POU-III class of neural transcription factors. This family member plays a role in inner ear development. The protein is thought to be involved in the mediation of epigenetic signals which induce striatal neuron-precursor differentiation. Mutations in this gene are associated with X chromosome-linked nonsyndromic mixed deafness. [provided by RefSeq, Dec 2012]

POU3F4 links:

ENSG00000279437 (HGNC:):

ENSG00000279437 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant X-83508515-G-A is Pathogenic according to our data. Variant chrX-83508515-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3250397.Status of the report is criteria_provided_single_submitter, 1 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.27950913). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU3F4	NM_000307.5 link	c.191G>A	p.Gly64Glu	missense_variant	1/1	ENST00000644024.2	NP_000298.3	P49335A0A2R8Y739

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU3F4	ENST00000644024.2 link	c.191G>A	p.Gly64Glu	missense_variant	1/1		NM_000307.5	ENSP00000495996.1		A0A2R8Y739
ENSG00000279437	ENST00000625081.1 link	n.700C>T		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000125

AC:

AN:

159911

Hom.:

AF XY:

0.00

AC XY:

AN XY:

50055

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000392

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:

0.0000146

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000459

AC:

AN:

1089456

Hom.:

Cov.:

AF XY:

0.00000281

AC XY:

AN XY:

356328

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000293

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:

0.00000239

Gnomad4 OTH exome

AF:

0.0000437

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

X-linked mixed hearing loss with perilymphatic gusher

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Laboratory of Prof. Karen Avraham, Tel Aviv University

Jun 05, 2024

A very rare variant predicted to be deleterious by most prediction programs -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Uncertain

0.090

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

0.98

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

.;D

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.28

T;T

MetaSVM

Uncertain

0.031

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-2.7

D;.

REVEL

Uncertain

0.43

Sift

Uncertain

0.0020

D;.

Sift4G

Uncertain

0.025

D;.

Vest4

0.41

MutPred

0.20

Gain of solvent accessibility (P = 0.0374);Gain of solvent accessibility (P = 0.0374);

MVP

0.93

MPC

1.6

ClinPred

0.49

GERP RS

4.8

gMVP

0.86

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