rs1236601406

Variant names:

• chr19-35269114-G-C
• rs1236601406
• NM_003367.4:c.13G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003367.4(USF2):​c.13G>C​(p.Asp5His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000084 (0 hom., cov: 16)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: USF2 NM_003367.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.24584031).

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.13G>C	p.Asp5His	missense	Exon 1 of 10	NP_003358.1	Q15853-1
	USF2	NM_207291.3		c.13G>C	p.Asp5His	missense	Exon 1 of 9	NP_997174.1	Q15853-3
	USF2	NM_001321150.2		c.13G>C	p.Asp5His	missense	Exon 1 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.13G>C	p.Asp5His	missense	Exon 1 of 10	ENSP00000222305.2	Q15853-1
	USF2	ENST00000343550.9	TSL:1	c.13G>C	p.Asp5His	missense	Exon 1 of 9	ENSP00000340633.4	Q15853-3
	USF2	ENST00000379134.7	TSL:1	c.13G>C	p.Asp5His	missense	Exon 1 of 8	ENSP00000368429.3	Q15853-4

Frequencies

GnomAD3 genomes AF: 0.00000837 AC: 1 AN: 119436 Hom.: 0 Cov.: 16

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000178

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 247126 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 126188

African (AFR) AF: 0.00 AC: 0 AN: 4650

American (AMR) AF: 0.00 AC: 0 AN: 3614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2796

East Asian (EAS) AF: 0.00 AC: 0 AN: 2290

South Asian (SAS) AF: 0.00 AC: 0 AN: 11110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1994

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 610

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 211490

Other (OTH) AF: 0.00 AC: 0 AN: 8572

GnomAD4 genome AF: 0.00000837 AC: 1 AN: 119436 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 57390

African (AFR) AF: 0.00 AC: 0 AN: 32414

American (AMR) AF: 0.00 AC: 0 AN: 12582

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2992

East Asian (EAS) AF: 0.00 AC: 0 AN: 3646

South Asian (SAS) AF: 0.00 AC: 0 AN: 3502

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5710

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 256

European-Non Finnish (NFE) AF: 0.0000178 AC: 1 AN: 56048

Other (OTH) AF: 0.00 AC: 0 AN: 1598

Alfa AF: 0.0000843 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	Pathogenic	0.76
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.017
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.40	N
LIST_S2	Uncertain	0.92	D
M_CAP	Pathogenic	0.96	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	0.19	D
MutationAssessor	Benign	1.6	L
PhyloP100		1.0
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.23
MutPred		0.20		Gain of catalytic residue at L2 (P = 0.1441)
MVP		0.41
MPC		1.4
ClinPred		0.54	D
GERP RS		2.0
PromoterAI		-0.043	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Varity_R		0.19
gMVP		0.26
Mutation Taster		=67/33	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

dbSNP: rs1236601406; hg19: chr19-35760017;