10-91908462-C-T

Variant names:

• chr10-91908462-C-T
• rs202089453
• NM_152429.5:c.508G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152429.5(FGFBP3):​c.508G>A​(p.Ala170Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000154 in 1,295,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. A170S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: FGFBP3 NM_152429.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540
• Publications: 0 publications found

Genes affected

FGFBP3 (HGNC:23428): (fibroblast growth factor binding protein 3) Enables fibroblast growth factor binding activity and heparin binding activity. Acts upstream of or within positive regulation of fibroblast growth factor receptor signaling pathway and positive regulation of vascular permeability. Located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000272817 (HGNC:58342):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.078069).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGFBP3	NM_152429.5	c.508G>A	p.Ala170Thr	missense_variant	Exon 2 of 2	ENST00000311575.6	NP_689642.3
FGFBP3-AS1	NR_199602.1	n.121+213C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGFBP3	ENST00000311575.6	c.508G>A	p.Ala170Thr	missense_variant	Exon 2 of 2	1	NM_152429.5	ENSP00000339067.3
ENSG00000272817	ENST00000610263.1	n.119+213C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000154 AC: 2 AN: 1295038 Hom.: 0 Cov.: 32 AF XY: 0.00000316 AC XY: 2 AN XY: 633824

African (AFR) AF: 0.00 AC: 0 AN: 25398

American (AMR) AF: 0.00 AC: 0 AN: 15392

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18944

East Asian (EAS) AF: 0.00 AC: 0 AN: 30660

South Asian (SAS) AF: 0.0000318 AC: 2 AN: 62970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4894

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1038454

Other (OTH) AF: 0.00 AC: 0 AN: 53152

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.90
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.054
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.018
Sift	Benign	0.23	T
Sift4G	Benign	0.23	T
Polyphen		0.23	B
Vest4		0.070
MutPred		0.31		Gain of phosphorylation at A170 (P = 8e-04);
MVP		0.30
ClinPred		0.11	T
GERP RS		1.8
Varity_R		0.027
gMVP		0.19
Mutation Taster		=99/1	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: rs202089453; hg19: chr10-93668219;