Variant rs2290477 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001009899.4(USF3):c.5896G>T(p.Ala1966Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0228 in 1,614,054 control chromosomes in the GnomAD database, including 1,041 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1966V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.024 ( 117 hom., cov: 32)

Exomes 𝑓: 0.023 ( 924 hom. )

Consequence

USF3
NM_001009899.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.99

Variant links:

Genes affected

USF3 (HGNC:30494): (upstream transcription factor family member 3) This gene encodes a large protein that contains a helix-loop-helix domain and a polyglutamine region. A deletion in the polyglutamine region was associated with risk for thyroid carcinoma. [provided by RefSeq, May 2017]

USF3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013995767).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USF3	NM_001009899.4 linkuse as main transcript	c.5896G>T	p.Ala1966Ser	missense_variant	7/7	ENST00000316407.9	NP_001009899.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
USF3	ENST00000316407.9 linkuse as main transcript	c.5896G>T	p.Ala1966Ser	missense_variant	7/7	5	NM_001009899.4	ENSP00000320794	P2
USF3	ENST00000491165.5 linkuse as main transcript	c.257-5936G>T		intron_variant		1		ENSP00000420752	A2
USF3	ENST00000496826.1 linkuse as main transcript	n.5850G>T		non_coding_transcript_exon_variant	3/3	1
USF3	ENST00000478658.1 linkuse as main transcript	c.5896G>T	p.Ala1966Ser	missense_variant	5/5	5		ENSP00000420721	P2

Frequencies

GnomAD3 genomes

AF:

0.0238

AC:

3627

AN:

152170

Hom.:

117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00466

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0487

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.0868

Gnomad FIN

AF:

0.0645

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0137

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.0444

AC:

11052

AN:

248978

Hom.:

446

AF XY:

0.0434

AC XY:

5867

AN XY:

135058

show subpopulations

Gnomad AFR exome

AF:

0.00452

Gnomad AMR exome

AF:

0.0942

Gnomad ASJ exome

AF:

0.0108

Gnomad EAS exome

AF:

0.118

Gnomad SAS exome

AF:

0.0803

Gnomad FIN exome

AF:

0.0659

Gnomad NFE exome

AF:

0.0128

Gnomad OTH exome

AF:

0.0336

GnomAD4 exome

AF:

0.0227

AC:

33147

AN:

1461766

Hom.:

924

Cov.:

AF XY:

0.0241

AC XY:

17557

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.00317

Gnomad4 AMR exome

AF:

0.0856

Gnomad4 ASJ exome

AF:

0.00960

Gnomad4 EAS exome

AF:

0.0923

Gnomad4 SAS exome

AF:

0.0782

Gnomad4 FIN exome

AF:

0.0660

Gnomad4 NFE exome

AF:

0.0121

Gnomad4 OTH exome

AF:

0.0250

GnomAD4 genome

AF:

0.0238

AC:

3617

AN:

152288

Hom.:

117

Cov.:

AF XY:

0.0278

AC XY:

2071

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00464

Gnomad4 AMR

AF:

0.0485

Gnomad4 ASJ

AF:

0.0115

Gnomad4 EAS

AF:

0.111

Gnomad4 SAS

AF:

0.0862

Gnomad4 FIN

AF:

0.0645

Gnomad4 NFE

AF:

0.0137

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0174

Hom.:

117

Bravo

AF:

0.0214

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.00934

AC:

ESP6500AA

AF:

0.00473

AC:

ESP6500EA

AF:

0.0123

AC:

104

ExAC

AF:

0.0412

AC:

4987

Asia WGS

AF:

0.0740

AC:

258

AN:

3478

EpiCase

AF:

0.0113

EpiControl

AF:

0.0103

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.88

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.54

T;.

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.37

PROVEAN

Benign

0.31

N;N

REVEL

Benign

0.031

Sift

Benign

0.41

T;T

Sift4G

Benign

0.64

T;T

Vest4

0.023

MPC

0.087

ClinPred

0.00075

GERP RS

3.7

gMVP

0.097

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over