rs756126359

Variant names:

• chr3-113655941-T-A
• rs756126359
• NM_001009899.4:c.5741A>T

Your query was ambiguous. Multiple possible variants found:

• chr3-113655941-T-A
• chr3-113655941-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001009899.4(USF3):​c.5741A>T​(p.Asn1914Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,874 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: 0.0000014 (0 hom.)
• Consequence: USF3 NM_001009899.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.57

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26350385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USF3	NM_001009899.4	c.5741A>T	p.Asn1914Ile	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.5741A>T	p.Asn1914Ile	missense_variant	Exon 7 of 7	5	NM_001009899.4	ENSP00000320794.4
USF3	ENST00000491165.5	c.257-6091A>T		intron_variant	Intron 6 of 6	1		ENSP00000420752.1
USF3	ENST00000496826.1	n.5695A>T		non_coding_transcript_exon_variant	Exon 3 of 3	1
USF3	ENST00000478658.1	c.5741A>T	p.Asn1914Ile	missense_variant	Exon 5 of 5	5		ENSP00000420721.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249476 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135348

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461874 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

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	0.26
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	23
DANN	Uncertain	0.98
Eigen	Benign	0.16
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D;.
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Benign	0.10
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0090	D;D
Vest4		0.54
MutPred		0.19		Gain of sheet (P = 0.0049);Gain of sheet (P = 0.0049);
MVP		0.043
MPC		0.46
ClinPred		0.92	D
GERP RS		3.1
gMVP		0.44

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: rs756126359; hg19: chr3-113374788;