Variant X-83508613-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000307.5(POU3F4):c.289C>G(p.Arg97Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,209,237 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 56 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., 8 hem., cov: 23)

Exomes 𝑓: 0.00013 ( 0 hom. 48 hem. )

Consequence

POU3F4
NM_000307.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.407

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013024986).

BP6

Variant X-83508613-C-G is Benign according to our data. Variant chrX-83508613-C-G is described in ClinVar as [Benign]. Clinvar id is 3021428.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 8 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POU3F4	NM_000307.5 linkuse as main transcript	c.289C>G	p.Arg97Gly	missense_variant	1/1	ENST00000644024.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU3F4	ENST00000644024.2 linkuse as main transcript	c.289C>G	p.Arg97Gly	missense_variant	1/1		NM_000307.5	P1
	ENST00000625081.1 linkuse as main transcript	n.602G>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.000196

AC:

AN:

112362

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

AN XY:

34522

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:

0.00323

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000291

AC:

AN:

175370

Hom.:

AF XY:

0.000324

AC XY:

AN XY:

61666

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:

0.00327

Gnomad NFE exome

AF:

0.0000259

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000129

AC:

141

AN:

1096875

Hom.:

Cov.:

AF XY:

0.000132

AC XY:

AN XY:

362411

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:

0.00330

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.000130

GnomAD4 genome

AF:

0.000196

AC:

AN:

112362

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

AN XY:

34522

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:

0.00323

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.000247

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 17, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

0.020

CADD

Benign

DANN

Uncertain

0.99

FATHMM_MKL

Uncertain

0.97

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.013

T;T

MetaSVM

Uncertain

0.060

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-2.7

D;.

REVEL

Uncertain

0.60

Sift

Benign

0.047

D;.

Sift4G

Benign

0.087

T;.

Vest4

0.52

MVP

0.97

MPC

2.4

ClinPred

0.20

GERP RS

5.0

gMVP

0.94

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