3-113655566-C-G

Position:

• chr3-113655566-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001009899.4(USF3):​c.6116G>C​(p.Arg2039Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: USF3 NM_001009899.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.38

Genes affected

USF3 (HGNC:30494): (upstream transcription factor family member 3) This gene encodes a large protein that contains a helix-loop-helix domain and a polyglutamine region. A deletion in the polyglutamine region was associated with risk for thyroid carcinoma. [provided by RefSeq, May 2017]

USF3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USF3	NM_001009899.4	c.6116G>C	p.Arg2039Pro	missense_variant	7/7	ENST00000316407.9	NP_001009899.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USF3	ENST00000316407.9	c.6116G>C	p.Arg2039Pro	missense_variant	7/7	5	NM_001009899.4	ENSP00000320794.4
USF3	ENST00000491165.5	c.257-5716G>C		intron_variant		1		ENSP00000420752.1
USF3	ENST00000496826.1	n.6070G>C		non_coding_transcript_exon_variant	3/3	1
USF3	ENST00000478658.1	c.6116G>C	p.Arg2039Pro	missense_variant	5/5	5		ENSP00000420721.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2024

The c.6116G>C (p.R2039P) alteration is located in exon 7 (coding exon 5) of the USF3 gene. This alteration results from a G to C substitution at nucleotide position 6116, causing the arginine (R) at amino acid position 2039 to be replaced by a proline (P). 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	0.97
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.91	D;.
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Benign	-0.88	T
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Uncertain	0.43
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.018	D;D
Vest4		0.96
MutPred		0.39		Gain of glycosylation at S2036 (P = 0.005);Gain of glycosylation at S2036 (P = 0.005);
MVP		0.10
MPC		0.58
ClinPred		0.97	D
GERP RS		5.8
gMVP		0.60

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.

Other links and lift over

hg19: chr3-113374413;