3-113655770-T-C

Variant names:

• chr3-113655770-T-C
• NM_001009899.4:c.5912A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001009899.4(USF3):​c.5912A>G​(p.Asn1971Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. 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: 0.784

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061073124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USF3	NM_001009899.4	c.5912A>G	p.Asn1971Ser	missense_variant	Exon 7 of 7	ENST00000316407.9	NP_001009899.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USF3	ENST00000316407.9	c.5912A>G	p.Asn1971Ser	missense_variant	Exon 7 of 7	5	NM_001009899.4	ENSP00000320794.4
USF3	ENST00000491165.5	c.257-5920A>G		intron_variant	Intron 6 of 6	1		ENSP00000420752.1
USF3	ENST00000496826.1	n.5866A>G		non_coding_transcript_exon_variant	Exon 3 of 3	1
USF3	ENST00000478658.1	c.5912A>G	p.Asn1971Ser	missense_variant	Exon 5 of 5	5		ENSP00000420721.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.5912A>G (p.N1971S) alteration is located in exon 7 (coding exon 5) of the USF3 gene. This alteration results from a A to G substitution at nucleotide position 5912, causing the asparagine (N) at amino acid position 1971 to be replaced by a serine (S). 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	Benign	0.061
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.67
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.77	T;.
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.061	T;T
MetaSVM	Benign	-0.95	T
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.068
Sift	Benign	0.074	T;T
Sift4G	Benign	1.0	T;T
Vest4		0.14
MutPred		0.12		Gain of glycosylation at S1972 (P = 0.0348);Gain of glycosylation at S1972 (P = 0.0348);
MVP		0.043
MPC		0.073
ClinPred		0.073	T
GERP RS		-2.3
gMVP		0.26

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: chr3-113374617;