NM_003367.4:c.185A>G

Variant names:

• chr19-35269656-A-G
• rs1303724217
• NM_003367.4:c.185A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_003367.4(USF2):​c.185A>G​(p.His62Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000506 in 1,382,682 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H62L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000051 (0 hom.)
• Consequence: USF2 NM_003367.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.73
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 7 AD gene.

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.185A>G	p.His62Arg	missense	Exon 3 of 10	NP_003358.1	Q15853-1
	USF2	NM_207291.3		c.185A>G	p.His62Arg	missense	Exon 3 of 9	NP_997174.1	Q15853-3
	USF2	NM_001321150.2		c.185A>G	p.His62Arg	missense	Exon 3 of 8	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.185A>G	p.His62Arg	missense	Exon 3 of 10	ENSP00000222305.2	Q15853-1
	USF2	ENST00000343550.9	TSL:1	c.185A>G	p.His62Arg	missense	Exon 3 of 9	ENSP00000340633.4	Q15853-3
	USF2	ENST00000379134.7	TSL:1	c.185A>G	p.His62Arg	missense	Exon 3 of 8	ENSP00000368429.3	Q15853-4

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD2 exomes AF: 0.00 AC: 0 AN: 226496 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000506 AC: 7 AN: 1382682 Hom.: 0 Cov.: 34 AF XY: 0.00000728 AC XY: 5 AN XY: 687076

African (AFR) AF: 0.00 AC: 0 AN: 30536

American (AMR) AF: 0.0000239 AC: 1 AN: 41832

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23192

East Asian (EAS) AF: 0.00 AC: 0 AN: 32254

South Asian (SAS) AF: 0.00 AC: 0 AN: 83694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5048

European-Non Finnish (NFE) AF: 0.00000563 AC: 6 AN: 1065114

Other (OTH) AF: 0.00 AC: 0 AN: 55234

GnomAD4 genome Cov.: 28

Alfa AF: 0.0000937 Hom.: 0

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	0.19
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.48	N
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.96	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.7
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.45
Sift	Benign	0.12	T
Sift4G	Benign	0.12	T
Polyphen		0.42	B
Vest4		0.45
MutPred		0.36		Gain of MoRF binding (P = 0.014)
MVP		0.57
MPC		1.8
ClinPred		0.76	D
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.25
Mutation Taster		=27/73	disease causing

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

dbSNP: rs1303724217; hg19: chr19-35760559;