9-130579741-G-A

Variant names:

• chr9-130579741-G-A
• rs953432114
• NM_003934.2:c.61G>A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3 BS2

The NM_003934.2(FUBP3):​c.61G>A​(p.Asp21Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000159 in 1,129,066 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: not found (cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: FUBP3 NM_003934.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.38

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]

LOC100272217 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.813
• BS2: High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUBP3	NM_003934.2	c.61G>A	p.Asp21Asn	missense_variant	Exon 1 of 19	ENST00000319725.10	NP_003925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUBP3	ENST00000319725.10	c.61G>A	p.Asp21Asn	missense_variant	Exon 1 of 19	1	NM_003934.2	ENSP00000318177.9
FUBP3	ENST00000467100.1	n.777G>A		non_coding_transcript_exon_variant	Exon 1 of 2	2
FUBP3	ENST00000650723.1	n.61G>A		non_coding_transcript_exon_variant	Exon 1 of 21			ENSP00000499109.1
FUBP3	ENST00000699747.1	n.61G>A		non_coding_transcript_exon_variant	Exon 1 of 19			ENSP00000514557.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000154 AC: 1 AN: 64940 Hom.: 0 AF XY: 0.0000274 AC XY: 1 AN XY: 36528

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000274

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000159 AC: 18 AN: 1129066 Hom.: 0 Cov.: 30 AF XY: 0.0000112 AC XY: 6 AN XY: 537868

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000877

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000170

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.61G>A (p.D21N) alteration is located in exon 1 (coding exon 1) of the FUBP3 gene. This alteration results from a G to A substitution at nucleotide position 61, causing the aspartic acid (D) at amino acid position 21 to be replaced by an asparagine (N). 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	0.80
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Benign	0.55	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.69	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.23
Sift	Benign	0.059	T
Sift4G	Uncertain	0.031	D
Polyphen		1.0	D
Vest4		0.53
MutPred		0.42		Gain of MoRF binding (P = 0.0312);
MVP		0.73
MPC		0.57
ClinPred		0.78	D
GERP RS		4.2
Varity_R		0.42
gMVP		0.62

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

Other links and lift over

dbSNP: rs953432114; hg19: chr9-133455128;