Variant rs74980526 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

The NM_001009899.4(USF3):c.6120C>T(p.Phe2040Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 1,614,150 control chromosomes in the GnomAD database, including 215 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0099 ( 13 hom., cov: 32)

Exomes 𝑓: 0.015 ( 202 hom. )

Consequence

USF3
NM_001009899.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.509

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP7

Synonymous conserved (PhyloP=0.509 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00993 (1512/152334) while in subpopulation NFE AF= 0.0167 (1139/68030). AF 95% confidence interval is 0.0159. There are 13 homozygotes in gnomad4. There are 717 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USF3	NM_001009899.4 link	c.6120C>T	p.Phe2040Phe	synonymous_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.6120C>T	p.Phe2040Phe	synonymous_variant	Exon 7 of 7	5	NM_001009899.4	ENSP00000320794.4	Q68DE3
USF3	ENST00000491165.5 link	c.257-5712C>T		intron_variant	Intron 6 of 6	1		ENSP00000420752.1	C9JBW0
USF3	ENST00000496826.1 link	n.6074C>T		non_coding_transcript_exon_variant	Exon 3 of 3	1
USF3	ENST00000478658.1 link	c.6120C>T	p.Phe2040Phe	synonymous_variant	Exon 5 of 5	5		ENSP00000420721.1	Q68DE3

Frequencies

GnomAD3 genomes

AF:

0.00993

AC:

1511

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00316

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00641

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0116

Gnomad FIN

AF:

0.00621

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0167

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.0102

AC:

2543

AN:

249378

Hom.:

AF XY:

0.0105

AC XY:

1418

AN XY:

135286

show subpopulations

Gnomad AFR exome

AF:

0.00258

Gnomad AMR exome

AF:

0.00498

Gnomad ASJ exome

AF:

0.00308

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.0115

Gnomad FIN exome

AF:

0.00696

Gnomad NFE exome

AF:

0.0153

Gnomad OTH exome

AF:

0.0116

GnomAD4 exome

AF:

0.0153

AC:

22334

AN:

1461816

Hom.:

202

Cov.:

AF XY:

0.0153

AC XY:

11129

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00239

Gnomad4 AMR exome

AF:

0.00519

Gnomad4 ASJ exome

AF:

0.00264

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0111

Gnomad4 FIN exome

AF:

0.00700

Gnomad4 NFE exome

AF:

0.0178

Gnomad4 OTH exome

AF:

0.0125

GnomAD4 genome

AF:

0.00993

AC:

1512

AN:

152334

Hom.:

Cov.:

AF XY:

0.00962

AC XY:

717

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00315

Gnomad4 AMR

AF:

0.00640

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0118

Gnomad4 FIN

AF:

0.00621

Gnomad4 NFE

AF:

0.0167

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.00921

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0173

EpiControl

AF:

0.0138

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

3.9

DANN

Benign

0.61

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