NM_001009899.4:c.6525G>A

Variant names:

• chr3-113655157-C-T
• rs760343877
• NM_001009899.4:c.6525G>A

Variant summary

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

The NM_001009899.4(USF3):​c.6525G>A​(p.Met2175Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: USF3 NM_001009899.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.74

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=0.3965815).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USF3	NM_001009899.4	c.6525G>A	p.Met2175Ile	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.6525G>A	p.Met2175Ile	missense_variant	Exon 7 of 7	5	NM_001009899.4	ENSP00000320794.4
USF3	ENST00000491165.5	c.257-5307G>A		intron_variant	Intron 6 of 6	1		ENSP00000420752.1
USF3	ENST00000496826.1	n.6479G>A		non_coding_transcript_exon_variant	Exon 3 of 3	1
USF3	ENST00000478658.1	c.6525G>A	p.Met2175Ile	missense_variant	Exon 5 of 5	5		ENSP00000420721.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000193 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Benign	0.96
Eigen	Benign	0.034
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.86	D;.
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.36	T;T
Vest4		0.74
MutPred		0.26		Gain of catalytic residue at P2177 (P = 0.0675);Gain of catalytic residue at P2177 (P = 0.0675);
MVP		0.19
MPC		0.50
ClinPred		0.72	D
GERP RS		5.6
gMVP		0.52

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

LitVar

Other links and lift over

dbSNP: rs760343877; hg19: chr3-113374004;