Genetic Variant NM_003367.4:c.83C>A (chr19-35269466-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003367.4(USF2):c.83C>A(p.Ala28Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000323 in 1,547,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A28V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

USF2
NM_003367.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.13

Publications

0 publications found

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:

ENSG00000307673 (HGNC:):

ENSG00000307673 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10427427).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003367.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USF2	NM_003367.4	MANE Select	c.83C>A	p.Ala28Glu	missense	Exon 2 of 10	NP_003358.1	Q15853-1
USF2	NM_207291.3		c.83C>A	p.Ala28Glu	missense	Exon 2 of 9	NP_997174.1	Q15853-3
USF2	NM_001321150.2		c.83C>A	p.Ala28Glu	missense	Exon 2 of 8	NP_001308079.1	Q15853-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USF2	ENST00000222305.8	TSL:1 MANE Select	c.83C>A	p.Ala28Glu	missense	Exon 2 of 10	ENSP00000222305.2	Q15853-1
USF2	ENST00000343550.9	TSL:1	c.83C>A	p.Ala28Glu	missense	Exon 2 of 9	ENSP00000340633.4	Q15853-3
USF2	ENST00000379134.7	TSL:1	c.83C>A	p.Ala28Glu	missense	Exon 2 of 8	ENSP00000368429.3	Q15853-4

Frequencies

GnomAD3 genomes

AF:

0.0000200

AC:

AN:

150168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000489

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000661

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:

0.00000143

AC:

AN:

1397264

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

693868

show subpopulations

African (AFR)

AF:

0.0000683

AC:

AN:

29282

American (AMR)

AF:

0.00

AC:

AN:

38696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24286

East Asian (EAS)

AF:

0.00

AC:

AN:

35020

South Asian (SAS)

AF:

0.00

AC:

AN:

79478

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41138

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4002

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1087836

Other (OTH)

AF:

0.00

AC:

AN:

57526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000200

AC:

AN:

150168

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73288

show subpopulations

African (AFR)

AF:

0.0000489

AC:

AN:

40916

American (AMR)

AF:

0.0000661

AC:

AN:

15118

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3446

East Asian (EAS)

AF:

0.00

AC:

AN:

5008

South Asian (SAS)

AF:

0.00

AC:

AN:

4788

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10206

Middle Eastern (MID)

AF:

0.00

AC:

AN:

300

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67406

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Uncertain

0.063

BayesDel_noAF

Benign

-0.15

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.077

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.82

M_CAP

Pathogenic

0.74

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.38

MutationAssessor

Benign

0.69

PhyloP100

2.1

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-0.46

REVEL

Uncertain

0.29

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.10

Vest4

0.38

MutPred

0.14

Loss of sheet (P = 0.0104)

MVP

0.21

MPC

0.95

ClinPred

0.12

GERP RS

1.8

PromoterAI

0.0044

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.13

gMVP

0.090

Mutation Taster

=83/17

polymorphism

(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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over