9-130622807-C-A

Variant names:

• chr9-130622807-C-A
• rs1434334245
• NM_003934.2:c.871C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003934.2(FUBP3):​c.871C>A​(p.Pro291Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000229 in 1,309,476 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P291S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: FUBP3 NM_003934.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.93
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.871C>A	p.Pro291Thr	missense	Exon 10 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.871C>A	p.Pro291Thr	missense	Exon 10 of 19	ENSP00000318177.9	Q96I24-1
	FUBP3	ENST00000964145.1		c.964C>A	p.Pro322Thr	missense	Exon 12 of 21	ENSP00000634204.1
	FUBP3	ENST00000936135.1		c.913C>A	p.Pro305Thr	missense	Exon 10 of 19	ENSP00000606194.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000229 AC: 3 AN: 1309476 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 657738

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29358

American (AMR) AF: 0.00 AC: 0 AN: 39348

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24446

East Asian (EAS) AF: 0.00 AC: 0 AN: 38288

South Asian (SAS) AF: 0.00 AC: 0 AN: 78000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52904

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5394

European-Non Finnish (NFE) AF: 0.00000304 AC: 3 AN: 986876

Other (OTH) AF: 0.00 AC: 0 AN: 54862

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.9
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.28
Sift	Benign	0.044	D
Sift4G	Uncertain	0.039	D
Polyphen		0.97	D
Vest4		0.32
MutPred		0.47		Gain of sheet (P = 0.039)
MVP		0.41
MPC		1.1
ClinPred		0.99	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.60
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs1434334245; hg19: chr9-133498194;