Variant 19-35269623-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_003367.4(USF2):c.152T>G(p.Ile51Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0017 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

USF2
NM_003367.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.53

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 Uncertain_significance. Variant got 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.817

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USF2	NM_003367.4 linkuse as main transcript	c.152T>G	p.Ile51Ser	missense_variant	3/10	ENST00000222305.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USF2	ENST00000222305.8 linkuse as main transcript	c.152T>G	p.Ile51Ser	missense_variant	3/10	1	NM_003367.4	P3	Q15853-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150358

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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:

0.0000980

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00170

AC:

2407

AN:

1416758

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

1105

AN XY:

705104

show subpopulations

Gnomad4 AFR exome

AF:

0.00163

Gnomad4 AMR exome

AF:

0.0000459

Gnomad4 ASJ exome

AF:

0.000913

Gnomad4 EAS exome

AF:

0.000497

Gnomad4 SAS exome

AF:

0.000585

Gnomad4 FIN exome

AF:

0.0000394

Gnomad4 NFE exome

AF:

0.00200

Gnomad4 OTH exome

AF:

0.00158

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000665

AC:

AN:

150358

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000980

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

May 15, 2023

The c.152T>G (p.I51S) alteration is located in exon 3 (coding exon 3) of the USF2 gene. This alteration results from a T to G substitution at nucleotide position 152, causing the isoleucine (I) at amino acid position 51 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

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Benign

0.71

LIST_S2

Pathogenic

0.98

D;D;D;D;D

M_CAP

Pathogenic

0.99

MetaRNN

Pathogenic

0.82

D;D;D;D;D

MetaSVM

Uncertain

0.51

MutationAssessor

Uncertain

2.5

M;M;M;M;.

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Pathogenic

0.95

PROVEAN

Uncertain

-2.6

D;N;.;N;.

REVEL

Pathogenic

0.74

Sift

Uncertain

0.010

D;D;.;D;.

Sift4G

Benign

0.099

T;D;D;T;D

Polyphen

0.99

D;D;.;.;D

Vest4

0.72

MutPred

0.42

.;.;.;.;Gain of disorder (P = 0.0034);

MVP

0.65

MPC

2.3

ClinPred

0.96

GERP RS

2.6

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.8

Varity_R

0.71

gMVP

0.52

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over