Variant 3-113655780-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_001009899.4(USF3):c.5902C>T(p.Arg1968Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000258 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00070 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

USF3
NM_001009899.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 6.88

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 Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.043644935).

BP6

Variant 3-113655780-G-A is Benign according to our data. Variant chr3-113655780-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2397634.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USF3	NM_001009899.4 link	c.5902C>T	p.Arg1968Cys	missense_variant	Exon 7 of 7	ENST00000316407.9	NP_001009899.3	Q68DE3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
USF3	ENST00000316407.9 link	c.5902C>T	p.Arg1968Cys	missense_variant	Exon 7 of 7	5	NM_001009899.4	ENSP00000320794.4	Q68DE3
USF3	ENST00000491165.5 link	c.257-5930C>T		intron_variant	Intron 6 of 6	1		ENSP00000420752.1	C9JBW0
USF3	ENST00000496826.1 link	n.5856C>T		non_coding_transcript_exon_variant	Exon 3 of 3	1
USF3	ENST00000478658.1 link	c.5902C>T	p.Arg1968Cys	missense_variant	Exon 5 of 5	5		ENSP00000420721.1	Q68DE3

Frequencies

GnomAD3 genomes

AF:

0.000703

AC:

107

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000229

AC:

AN:

249034

Hom.:

AF XY:

0.000185

AC XY:

AN XY:

135102

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.000407

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:

0.000159

Gnomad OTH exome

AF:

0.000993

GnomAD4 exome

AF:

0.000212

AC:

310

AN:

1461800

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

147

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.00203

Gnomad4 AMR exome

AF:

0.000515

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000174

Gnomad4 OTH exome

AF:

0.000281

GnomAD4 genome

AF:

0.000703

AC:

107

AN:

152260

Hom.:

Cov.:

AF XY:

0.000658

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00176

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000290

Hom.:

Bravo

AF:

0.000695

ESP6500AA

AF:

0.00119

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.000355

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000415

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 18, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.5902C>T (p.R1968C) alteration is located in exon 7 (coding exon 5) of the USF3 gene. This alteration results from a C to T substitution at nucleotide position 5902, causing the arginine (R) at amino acid position 1968 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

USF3: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Pathogenic

1.0

Eigen

Uncertain

0.63

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;.

M_CAP

Benign

0.012

MetaRNN

Benign

0.044

T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-2.5

N;N

REVEL

Benign

0.26

Sift

Uncertain

0.0020

D;D

Sift4G

Benign

0.079

T;T

Vest4

0.69

MVP

0.043

MPC

0.56

ClinPred

0.031

GERP RS

5.6

gMVP

0.32

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