3-113651163-G-T

Variant names:

• chr3-113651163-G-T
• rs1026364
• NM_001009899.4:c.*3781C>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001009899.4(USF3):​c.*3781C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,894 control chromosomes in the GnomAD database, including 10,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10407 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: USF3 NM_001009899.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.689

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 3-113651163-G-T is Benign according to our data. Variant chr3-113651163-G-T is described in ClinVar as [Benign]. Clinvar id is 1279888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USF3	NM_001009899.4	c.*3781C>A		3_prime_UTR_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	c.*3781C>A		3_prime_UTR_variant	Exon 7 of 7	5	NM_001009899.4	ENSP00000320794.4
USF3	ENST00000491165.5	c.257-1313C>A		intron_variant	Intron 6 of 6	1		ENSP00000420752.1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56174 AN: 151776 Hom.: 10393 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.340

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.370 AC: 56214 AN: 151894 Hom.: 10407 Cov.: 32 AF XY: 0.371 AC XY: 27530 AN XY: 74224

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.337

Alfa AF: 0.339 Hom.: 15030

Bravo AF: 0.364

Asia WGS AF: 0.303 AC: 1052 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 15, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 31883164, 22504420) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.42

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: rs1026364; hg19: chr3-113370010;