Variant chr19-35269977-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003367.4(USF2):c.403C>T(p.Pro135Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000489 in 1,344,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00051 ( 0 hom. )

Consequence

USF2
NM_003367.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.815

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.034547657).

BS2

High AC in GnomAd4 at 44 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USF2	NM_003367.4 linkuse as main transcript	c.403C>T	p.Pro135Ser	missense_variant	4/10	ENST00000222305.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USF2	ENST00000222305.8 linkuse as main transcript	c.403C>T	p.Pro135Ser	missense_variant	4/10	1	NM_003367.4	P3	Q15853-1

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000388

AC:

AN:

2580

Hom.:

AF XY:

0.000722

AC XY:

AN XY:

1386

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000812

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000515

AC:

614

AN:

1192546

Hom.:

Cov.:

AF XY:

0.000515

AC XY:

296

AN XY:

574744

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000404

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000527

Gnomad4 FIN exome

AF:

0.000321

Gnomad4 NFE exome

AF:

0.000544

Gnomad4 OTH exome

AF:

0.000651

GnomAD4 genome

AF:

0.000289

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000582

Hom.:

Bravo

AF:

0.000348

ExAC

AF:

0.000125

AC:

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

Aug 30, 2021

The c.403C>T (p.P135S) alteration is located in exon 4 (coding exon 4) of the USF2 gene. This alteration results from a C to T substitution at nucleotide position 403, causing the proline (P) at amino acid position 135 to be replaced by a serine (S). 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

0.063

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.076

T;.;T

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.64

T;T;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.035

T;T;T

MetaSVM

Benign

-0.49

MutationAssessor

Benign

0.90

L;L;.

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.26

N;.;.

REVEL

Benign

0.25

Sift

Uncertain

0.025

D;.;.

Sift4G

Benign

0.74

T;T;T

Polyphen

0.035

B;.;B

Vest4

0.071

MutPred

0.19

.;.;Loss of catalytic residue at P132 (P = 0.0193);

MVP

0.30

MPC

0.82

ClinPred

0.040

GERP RS

1.3

Varity_R

0.10

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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