chr10-91908462-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152429.5(FGFBP3):​c.508G>T​(p.Ala170Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000166 in 1,447,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: FGFBP3 NM_152429.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0540
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014004052).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGFBP3	NM_152429.5	c.508G>T	p.Ala170Ser	missense_variant	Exon 2 of 2	ENST00000311575.6	NP_689642.3
FGFBP3-AS1	NR_199602.1	n.121+213C>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGFBP3	ENST00000311575.6	c.508G>T	p.Ala170Ser	missense_variant	Exon 2 of 2	1	NM_152429.5	ENSP00000339067.3
ENSG00000272817	ENST00000610263.1	n.119+213C>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152118 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000682 AC: 5 AN: 73284 AF XY: 0.0000727

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00113

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000131 AC: 17 AN: 1295038 Hom.: 0 Cov.: 32 AF XY: 0.0000158 AC XY: 10 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: 0.000522 AC: 16 AN: 30660

South Asian (SAS) AF: 0.00 AC: 0 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: 0.0000188 AC: 1 AN: 53152

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152230 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74432

African (AFR) AF: 0.00 AC: 0 AN: 41562

American (AMR) AF: 0.0000654 AC: 1 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67980

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000526 AC: 6

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.508G>T (p.A170S) alteration is located in exon 2 (coding exon 1) of the FGFBP3 gene. This alteration results from a G to T substitution at nucleotide position 508, causing the alanine (A) at amino acid position 170 to be replaced by a serine (S). 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	0.078
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.8
DANN	Benign	0.92
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.054
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.010
Sift	Benign	0.20	T
Sift4G	Benign	0.42	T
Polyphen		0.23	B
Vest4		0.061
MVP		0.38
ClinPred		0.027	T
GERP RS		1.8
Varity_R		0.033
gMVP		0.19
Mutation Taster		=98/2	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;