9-130623656-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003934.2(FUBP3):​c.920C>T​(p.Pro307Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000341 in 1,613,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

FUBP3
NM_003934.2 missense

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.07
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.20095465).
BS2
High AC in GnomAdExome4 at 53 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FUBP3NM_003934.2 linkc.920C>T p.Pro307Leu missense_variant Exon 11 of 19 ENST00000319725.10 NP_003925.1 Q96I24-1A0A024R8A7
FUBP3XM_005272232.3 linkc.920C>T p.Pro307Leu missense_variant Exon 11 of 18 XP_005272289.1
FUBP3XM_011519172.4 linkc.920C>T p.Pro307Leu missense_variant Exon 11 of 17 XP_011517474.1
FUBP3XR_007061369.1 linkn.1024C>T non_coding_transcript_exon_variant Exon 11 of 15

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FUBP3ENST00000319725.10 linkc.920C>T p.Pro307Leu missense_variant Exon 11 of 19 1 NM_003934.2 ENSP00000318177.9 Q96I24-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152178
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000481
AC:
12
AN:
249462
Hom.:
0
AF XY:
0.0000665
AC XY:
9
AN XY:
135346
show subpopulations
Gnomad AFR exome
AF:
0.0000646
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000363
AC:
53
AN:
1461658
Hom.:
0
Cov.:
30
AF XY:
0.0000550
AC XY:
40
AN XY:
727144
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000255
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000225
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152296
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000370
Hom.:
0
ExAC
AF:
0.0000744
AC:
9

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 07, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.920C>T (p.P307L) alteration is located in exon 11 (coding exon 11) of the FUBP3 gene. This alteration results from a C to T substitution at nucleotide position 920, causing the proline (P) at amino acid position 307 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.071
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.29
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T
Eigen
Uncertain
0.41
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
D
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.20
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Uncertain
2.6
M
PrimateAI
Uncertain
0.67
T
PROVEAN
Pathogenic
-7.5
D
REVEL
Benign
0.24
Sift
Uncertain
0.0090
D
Sift4G
Benign
0.18
T
Polyphen
0.60
P
Vest4
0.55
MVP
0.44
MPC
0.75
ClinPred
0.42
T
GERP RS
5.5
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6
Varity_R
0.56
gMVP
0.86

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs528138061; hg19: chr9-133499043; COSMIC: COSV60513044; COSMIC: COSV60513044; API