Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001009899.4(USF3):c.*3781C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,894 control chromosomes in the GnomAD database, including 10,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10407 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

USF3
NM_001009899.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.689

Publications

38 publications found

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 Gene-Disease associations (from GenCC):

Cowden disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

USF3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 3-113651163-G-T is Benign according to our data. Variant chr3-113651163-G-T is described in ClinVar as Benign. ClinVar VariationId is 1279888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009899.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USF3	NM_001009899.4	MANE Select	c.*3781C>A		3_prime_UTR	Exon 7 of 7	NP_001009899.3
	USF3	NR_111981.2		n.664-1313C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USF3	ENST00000316407.9	TSL:5 MANE Select	c.*3781C>A		3_prime_UTR	Exon 7 of 7	ENSP00000320794.4
	USF3	ENST00000491165.5	TSL:1	c.257-1313C>A		intron	N/A	ENSP00000420752.1

Frequencies

GnomAD3 genomes

AF:

0.370

AC:

56174

AN:

151776

Hom.:

10393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.412

Gnomad AMI

AF:

0.456

Gnomad AMR

AF:

0.332

Gnomad ASJ

AF:

0.257

Gnomad EAS

AF:

0.343

Gnomad SAS

AF:

0.289

Gnomad FIN

AF:

0.438

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.340

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.370

AC:

56214

AN:

151894

Hom.:

10407

Cov.:

AF XY:

0.371

AC XY:

27530

AN XY:

74224

show subpopulations

African (AFR)

AF:

0.413

AC:

17109

AN:

41446

American (AMR)

AF:

0.332

AC:

5065

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.257

AC:

891

AN:

3462

East Asian (EAS)

AF:

0.342

AC:

1771

AN:

5176

South Asian (SAS)

AF:

0.288

AC:

1389

AN:

4816

European-Finnish (FIN)

AF:

0.438

AC:

4593

AN:

10482

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.356

AC:

24191

AN:

67938

Other (OTH)

AF:

0.337

AC:

708

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1854

3708

5561

7415

9269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

546

1092

1638

2184

2730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.351

Hom.:

37624

Bravo

AF:

0.364

Asia WGS

AF:

0.303

AC:

1052

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

1.3

(source)

DANN

Benign

0.42

PhyloP100

0.69

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_001009899.4:c.*3781C>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over