Variant 2-104855597-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_006236.3(POU3F3):c.87T>C(p.Ala29Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 963,106 control chromosomes in the GnomAD database, including 198,956 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.70 ( 28477 hom., cov: 17)

Exomes 𝑓: 0.64 ( 170479 hom. )

Consequence

POU3F3
NM_006236.3 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.27

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-104855597-T-C is Benign according to our data. Variant chr2-104855597-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3056811.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.27 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU3F3	NM_006236.3 linkuse as main transcript	c.87T>C	p.Ala29Ala	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.87T>C	p.Ala29Ala	synonymous_variant	1/1	6	NM_006236.3	ENSP00000355001.2		P20264

Frequencies

GnomAD3 genomes

AF:

0.703

AC:

86232

AN:

122746

Hom.:

28473

Cov.:

show subpopulations

Gnomad AFR

AF:

0.700

Gnomad AMI

AF:

0.632

Gnomad AMR

AF:

0.754

Gnomad ASJ

AF:

0.722

Gnomad EAS

AF:

0.911

Gnomad SAS

AF:

0.639

Gnomad FIN

AF:

0.699

Gnomad MID

AF:

0.780

Gnomad NFE

AF:

0.681

Gnomad OTH

AF:

0.724

GnomAD3 exomes

AF:

0.615

AC:

3336

AN:

5426

Hom.:

1020

AF XY:

0.612

AC XY:

2251

AN XY:

3676

show subpopulations

Gnomad AFR exome

AF:

0.667

Gnomad AMR exome

AF:

0.705

Gnomad ASJ exome

AF:

0.653

Gnomad EAS exome

AF:

0.958

Gnomad SAS exome

AF:

0.511

Gnomad FIN exome

AF:

0.643

Gnomad NFE exome

AF:

0.650

Gnomad OTH exome

AF:

0.593

GnomAD4 exome

AF:

0.636

AC:

534793

AN:

840360

Hom.:

170479

Cov.:

AF XY:

0.635

AC XY:

247951

AN XY:

390318

show subpopulations

Gnomad4 AFR exome

AF:

0.637

Gnomad4 AMR exome

AF:

0.724

Gnomad4 ASJ exome

AF:

0.666

Gnomad4 EAS exome

AF:

0.901

Gnomad4 SAS exome

AF:

0.521

Gnomad4 FIN exome

AF:

0.607

Gnomad4 NFE exome

AF:

0.637

Gnomad4 OTH exome

AF:

0.642

GnomAD4 genome

AF:

0.703

AC:

86238

AN:

122746

Hom.:

28477

Cov.:

AF XY:

0.703

AC XY:

41611

AN XY:

59174

show subpopulations

Gnomad4 AFR

AF:

0.700

Gnomad4 AMR

AF:

0.754

Gnomad4 ASJ

AF:

0.722

Gnomad4 EAS

AF:

0.911

Gnomad4 SAS

AF:

0.639

Gnomad4 FIN

AF:

0.699

Gnomad4 NFE

AF:

0.681

Gnomad4 OTH

AF:

0.726

Alfa

AF:

0.431

Hom.:

817

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

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

-0.82

CADD

Benign

DANN

Benign

0.54

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