Variant 2-104855531-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_006236.3(POU3F3):c.21C>T(p.Asn7Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00315 in 1,045,068 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 23)

Exomes 𝑓: 0.0034 ( 5 hom. )

Consequence

POU3F3
NM_006236.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.748

Variant links:

Genes affected

POU3F3 (HGNC:9216): (POU class 3 homeobox 3) This gene encodes a POU-domain containing protein that functions as a transcription factor. The encoded protein recognizes an octamer sequence in the DNA of target genes. This protein may play a role in development of the nervous system. [provided by RefSeq, Apr 2015]

POU3F3 links:

ENSG00000269707 (HGNC:):

ENSG00000269707 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 2-104855531-C-T is Benign according to our data. Variant chr2-104855531-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2651213.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.748 with no splicing effect.

BS2

High AC in GnomAd4 at 238 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU3F3	NM_006236.3 linkuse as main transcript	c.21C>T	p.Asn7Asn	synonymous_variant	1/1	ENST00000361360.4	NP_006227.1	P20264

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU3F3	ENST00000361360.4 linkuse as main transcript	c.21C>T	p.Asn7Asn	synonymous_variant	1/1	6	NM_006236.3	ENSP00000355001.2		P20264

Frequencies

GnomAD3 genomes

AF:

0.00168

AC:

238

AN:

141492

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000511

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00251

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:

0.00276

Gnomad OTH

AF:

0.00207

GnomAD3 exomes

AF:

0.00102

AC:

AN:

36124

Hom.:

AF XY:

0.000828

AC XY:

AN XY:

21748

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00152

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000116

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00193

Gnomad OTH exome

AF:

0.00199

GnomAD4 exome

AF:

0.00338

AC:

3054

AN:

903548

Hom.:

Cov.:

AF XY:

0.00327

AC XY:

1411

AN XY:

431484

show subpopulations

Gnomad4 AFR exome

AF:

0.000295

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000974

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00370

Gnomad4 OTH exome

AF:

0.00243

GnomAD4 genome

AF:

0.00168

AC:

238

AN:

141520

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

AN XY:

68658

show subpopulations

Gnomad4 AFR

AF:

0.000510

Gnomad4 AMR

AF:

0.00251

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00276

Gnomad4 OTH

AF:

0.00206

Alfa

AF:

0.00194

Hom.:

Bravo

AF:

0.00167

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2024

POU3F3: BP4, BS1 -

POU3F3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 23, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

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