chr9-130620408-C-T

Variant names:

• chr9-130620408-C-T
• rs1339975663
• NM_003934.2:c.721C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3 BS2

The NM_003934.2(FUBP3):​c.721C>T​(p.Arg241Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,605,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: FUBP3 NM_003934.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.41
• Publications: 1 publications found

Genes affected

FUBP3 (HGNC:4005): (far upstream element binding protein 3) Enables single-stranded DNA binding activity. Involved in positive regulation of gene expression; positive regulation of transcription, DNA-templated; and transcription, DNA-templated. Acts upstream of or within positive regulation of transcription by RNA polymerase II. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.77
• BS2: High AC in GnomAd4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003934.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUBP3	NM_003934.2	MANE Select	c.721C>T	p.Arg241Trp	missense	Exon 9 of 19	NP_003925.1	Q96I24-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FUBP3	ENST00000319725.10	TSL:1 MANE Select	c.721C>T	p.Arg241Trp	missense	Exon 9 of 19	ENSP00000318177.9	Q96I24-1
	FUBP3	ENST00000964145.1		c.814C>T	p.Arg272Trp	missense	Exon 11 of 21	ENSP00000634204.1
	FUBP3	ENST00000936135.1		c.763C>T	p.Arg255Trp	missense	Exon 9 of 19	ENSP00000606194.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152034 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000410 AC: 1 AN: 243702 AF XY: 0.00000756

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 FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000151 AC: 22 AN: 1453184 Hom.: 0 Cov.: 27 AF XY: 0.0000111 AC XY: 8 AN XY: 722864

African (AFR) AF: 0.00 AC: 0 AN: 33198

American (AMR) AF: 0.00 AC: 0 AN: 43498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.0000510 AC: 2 AN: 39226

South Asian (SAS) AF: 0.00 AC: 0 AN: 84730

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.0000154 AC: 17 AN: 1107308

Other (OTH) AF: 0.00 AC: 0 AN: 60064

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152034 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74256

African (AFR) AF: 0.0000966 AC: 4 AN: 41388

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.075	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.4
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.047	D
Polyphen		1.0	D
Vest4		0.60
MutPred		0.58		Loss of disorder (P = 0.0072)
MVP		0.58
MPC		1.4
ClinPred		0.99	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.83
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1339975663; hg19: chr9-133495795; COSMIC: COSV60516364; COSMIC: COSV60516364;