3-113655636-G-C

Variant names:

• chr3-113655636-G-C
• NM_001009899.4:c.6046C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001009899.4(USF3):​c.6046C>G​(p.Leu2016Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: USF3 NM_001009899.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.39

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34492314).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USF3	NM_001009899.4	c.6046C>G	p.Leu2016Val	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.6046C>G	p.Leu2016Val	missense_variant	Exon 7 of 7	5	NM_001009899.4	ENSP00000320794.4
USF3	ENST00000491165.5	c.257-5786C>G		intron_variant	Intron 6 of 6	1		ENSP00000420752.1
USF3	ENST00000496826.1	n.6000C>G		non_coding_transcript_exon_variant	Exon 3 of 3	1
USF3	ENST00000478658.1	c.6046C>G	p.Leu2016Val	missense_variant	Exon 5 of 5	5		ENSP00000420721.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461600 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727046

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	1.0
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	D;.
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.17	T;T
Vest4		0.54
MutPred		0.14		Gain of glycosylation at S2021 (P = 0.0241);Gain of glycosylation at S2021 (P = 0.0241);
MVP		0.15
MPC		0.48
ClinPred		0.80	D
GERP RS		6.0
gMVP		0.29

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: chr3-113374483;