Variant 3-113655044-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001009899.4(USF3):c.6638T>C(p.Ile2213Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,614,070 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

USF3
NM_001009899.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.95

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USF3	NM_001009899.4 link	c.6638T>C	p.Ile2213Thr	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.6638T>C	p.Ile2213Thr	missense_variant	Exon 7 of 7	5	NM_001009899.4	ENSP00000320794.4	Q68DE3
USF3	ENST00000491165.5 link	c.257-5194T>C		intron_variant	Intron 6 of 6	1		ENSP00000420752.1	C9JBW0
USF3	ENST00000496826.1 link	n.6592T>C		non_coding_transcript_exon_variant	Exon 3 of 3	1
USF3	ENST00000478658.1 link	c.6638T>C	p.Ile2213Thr	missense_variant	Exon 5 of 5	5		ENSP00000420721.1	Q68DE3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 27, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.6638T>C (p.I2213T) alteration is located in exon 7 (coding exon 5) of the USF3 gene. This alteration results from a T to C substitution at nucleotide position 6638, causing the isoleucine (I) at amino acid position 2213 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Uncertain

0.078

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

D;.

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.46

T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.25

Sift

Uncertain

0.0020

D;D

Sift4G

Benign

0.13

T;T

Vest4

0.80

MutPred

0.26

Loss of stability (P = 0.0065);Loss of stability (P = 0.0065);

MVP

0.043

MPC

0.54

ClinPred

0.89

GERP RS

5.6

gMVP

0.45

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