NM_003934.2:c.1183C>T

Variant names:

• chr9-130630693-C-T
• rs886648631
• NM_003934.2:c.1183C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BS2

The NM_003934.2(FUBP3):​c.1183C>T​(p.Pro395Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,446,428 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: FUBP3 NM_003934.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS2: High AC in GnomAdExome4 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.1183C>T	p.Pro395Ser	missense	Exon 13 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.1183C>T	p.Pro395Ser	missense	Exon 13 of 19	ENSP00000318177.9	Q96I24-1
	FUBP3	ENST00000964145.1		c.1276C>T	p.Pro426Ser	missense	Exon 15 of 21	ENSP00000634204.1
	FUBP3	ENST00000936135.1		c.1225C>T	p.Pro409Ser	missense	Exon 13 of 19	ENSP00000606194.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000346 AC: 5 AN: 1446428 Hom.: 0 Cov.: 31 AF XY: 0.00000278 AC XY: 2 AN XY: 719752

African (AFR) AF: 0.00 AC: 0 AN: 32076

American (AMR) AF: 0.00 AC: 0 AN: 42564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25482

East Asian (EAS) AF: 0.00 AC: 0 AN: 37746

South Asian (SAS) AF: 0.00 AC: 0 AN: 84922

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53140

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00000452 AC: 5 AN: 1105104

Other (OTH) AF: 0.00 AC: 0 AN: 59682

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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	0.12
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.5	L
PhyloP100		7.9
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Uncertain	0.34
Sift	Benign	0.13	T
Sift4G	Benign	0.10	T
Polyphen		1.0	D
Vest4		0.56
MutPred		0.38		Loss of catalytic residue at P395 (P = 0.0121)
MVP		0.54
MPC		1.4
ClinPred		0.99	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.71
Mutation Taster		=50/50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs886648631; hg19: chr9-133506080;