9-130616474-G-T

Variant names:

• chr9-130616474-G-T
• NM_003934.2:c.524G>T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_003934.2(FUBP3):​c.524G>T​(p.Gly175Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FUBP3 NM_003934.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.92

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

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.98

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUBP3	NM_003934.2	c.524G>T	p.Gly175Val	missense_variant	Exon 7 of 19	ENST00000319725.10	NP_003925.1
FUBP3	XM_005272232.3	c.524G>T	p.Gly175Val	missense_variant	Exon 7 of 18		XP_005272289.1
FUBP3	XM_011519172.4	c.524G>T	p.Gly175Val	missense_variant	Exon 7 of 17		XP_011517474.1
FUBP3	XR_007061369.1	n.628G>T		non_coding_transcript_exon_variant	Exon 7 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUBP3	ENST00000319725.10	c.524G>T	p.Gly175Val	missense_variant	Exon 7 of 19	1	NM_003934.2	ENSP00000318177.9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.524G>T (p.G175V) alteration is located in exon 7 (coding exon 7) of the FUBP3 gene. This alteration results from a G to T substitution at nucleotide position 524, causing the glycine (G) at amino acid position 175 to be replaced by a valine (V). 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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.98
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	0.17	D
MutationAssessor	Pathogenic	4.1	H
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-8.5	D
REVEL	Pathogenic	0.80
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.96
MutPred		0.92		Gain of sheet (P = 0.0827);
MVP		0.83
MPC		1.6
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.97
gMVP		0.98

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-133491861;