chr3-113655356-G-A

Position:

• chr3-113655356-G-A

Variant summary

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

The NM_001009899.4(USF3):​c.6326C>T​(p.Ser2109Phe) 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: 9.60

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.6326C>T	p.Ser2109Phe	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.6326C>T	p.Ser2109Phe	missense_variant	7/7	5	NM_001009899.4	ENSP00000320794.4
USF3	ENST00000491165.5	c.257-5506C>T		intron_variant		1		ENSP00000420752.1
USF3	ENST00000496826.1	n.6280C>T		non_coding_transcript_exon_variant	3/3	1
USF3	ENST00000478658.1	c.6326C>T	p.Ser2109Phe	missense_variant	5/5	5		ENSP00000420721.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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 03, 2022

The c.6326C>T (p.S2109F) alteration is located in exon 7 (coding exon 5) of the USF3 gene. This alteration results from a C to T substitution at nucleotide position 6326, causing the serine (S) at amino acid position 2109 to be replaced by a phenylalanine (F). 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	0.80
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	28
DANN	Uncertain	1.0
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D;.
M_CAP	Benign	0.061	D
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Benign	-0.90	T
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.5	D;D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Vest4		0.83
MutPred		0.28		Loss of glycosylation at P2113 (P = 0.0092);Loss of glycosylation at P2113 (P = 0.0092);
MVP		0.068
MPC		0.50
ClinPred		0.96	D
GERP RS		5.3
gMVP		0.67

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: chr3-113374203;