19-35269923-G-C

Variant names:

• chr19-35269923-G-C
• NM_003367.4:c.349G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003367.4(USF2):​c.349G>C​(p.Val117Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: USF2 NM_003367.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.23
• Publications: 0 publications found

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]

ENSG00000307673 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31020772).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USF2	NM_003367.4	MANE Select	c.349G>C	p.Val117Leu	missense	Exon 4 of 10	NP_003358.1	Q15853-1
	USF2	NM_207291.3		c.228+224G>C		intron	N/A	NP_997174.1	Q15853-3
	USF2	NM_001321150.2		c.228+224G>C		intron	N/A	NP_001308079.1	Q15853-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USF2	ENST00000222305.8	TSL:1 MANE Select	c.349G>C	p.Val117Leu	missense	Exon 4 of 10	ENSP00000222305.2	Q15853-1
	USF2	ENST00000343550.9	TSL:1	c.228+224G>C		intron	N/A	ENSP00000340633.4	Q15853-3
	USF2	ENST00000379134.7	TSL:1	c.228+224G>C		intron	N/A	ENSP00000368429.3	Q15853-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.31	T
MetaSVM	Uncertain	0.26	D
MutationAssessor	Benign	1.1	L
PhyloP100		5.2
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.48	N
REVEL	Uncertain	0.51
Sift	Benign	0.079	T
Sift4G	Benign	0.13	T
Polyphen		0.98	D
Vest4		0.33
MutPred		0.21		Loss of sheet (P = 0.0457)
MVP		0.49
MPC		0.80
ClinPred		0.75	D
GERP RS		3.5
PromoterAI		0.061	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.30
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

hg19: chr19-35760826;