Variant chr19-35269139-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003367.4(USF2):c.38C>T(p.Ser13Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000075 ( 0 hom., cov: 18)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

USF2
NM_003367.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.683

Variant links:

Genes affected

USF2 (HGNC:12594): (upstream transcription factor 2, c-fos interacting) This gene encodes a member of the basic helix-loop-helix leucine zipper family of transcription factors. The encoded protein can activate transcription through pyrimidine-rich initiator (Inr) elements and E-box motifs and is involved in regulating multiple cellular processes. [provided by RefSeq, Mar 2016]

USF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13537088).

BS2

High AC in GnomAdExome4 at 45 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USF2	NM_003367.4 linkuse as main transcript	c.38C>T	p.Ser13Leu	missense_variant	1/10	ENST00000222305.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USF2	ENST00000222305.8 linkuse as main transcript	c.38C>T	p.Ser13Leu	missense_variant	1/10	1	NM_003367.4	P3	Q15853-1

Frequencies

GnomAD3 genomes

AF:

0.00000754

AC:

AN:

132674

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000273

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:

0.0000533

AC:

AN:

844642

Hom.:

Cov.:

AF XY:

0.0000596

AC XY:

AN XY:

402818

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000196

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000586

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000753

AC:

AN:

132744

Hom.:

Cov.:

AF XY:

0.0000155

AC XY:

AN XY:

64394

show subpopulations

Gnomad4 AFR

AF:

0.0000272

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 18, 2023

The c.38C>T (p.S13L) alteration is located in exon 1 (coding exon 1) of the USF2 gene. This alteration results from a C to T substitution at nucleotide position 38, causing the serine (S) at amino acid position 13 to be replaced by a leucine (L). 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

Benign

0.24

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.97

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.74

T;T;T;T;T

M_CAP

Pathogenic

0.97

MetaRNN

Benign

0.14

T;T;T;T;T

MetaSVM

Benign

-0.52

MutationAssessor

Benign

0.69

N;N;N;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.42

N;N;.;N;.

REVEL

Benign

0.24

Sift

Benign

0.32

T;T;.;T;.

Sift4G

Benign

0.26

T;T;T;T;T

Polyphen

0.71

P;B;.;.;B

Vest4

0.11

MutPred

0.24

.;.;.;.;Loss of glycosylation at S11 (P = 0.004);

MVP

0.17

MPC

0.72

ClinPred

0.082

GERP RS

-1.0

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.3

Varity_R

0.068

gMVP

0.16

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