17-75923516-T-G

Position:

• chr17-75923516-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001319193.2(FBF1):​c.1094A>C​(p.Glu365Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FBF1 NM_001319193.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.19

Genes affected

FBF1 (HGNC:24674): (Fas binding factor 1) Involved in apical junction assembly and establishment of epithelial cell polarity. Acts upstream of or within cilium assembly. Located in centriole; centrosome; and spindle pole. Part of ciliary transition fiber. Colocalizes with apical junction complex and keratin filament. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08335152).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBF1	NM_001319193.2	c.1094A>C	p.Glu365Ala	missense_variant	14/30	ENST00000636174.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBF1	ENST00000636174.2	c.1094A>C	p.Glu365Ala	missense_variant	14/30	5	NM_001319193.2	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453308 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 722166

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.1049A>C (p.E350A) alteration is located in exon 13 (coding exon 12) of the FBF1 gene. This alteration results from a A to C substitution at nucleotide position 1049, causing the glutamic acid (E) at amino acid position 350 to be replaced by an alanine (A). 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	0.15
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.069	T;T;.
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.68	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.083	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.29	T
Sift4G	Benign	0.14	T;T;.
Polyphen		0.33	B;.;B
Vest4		0.088
MutPred		0.15		Loss of solvent accessibility (P = 0.002);.;.;
MVP		0.18
ClinPred		0.36	T
GERP RS		2.9
Varity_R		0.097
gMVP		0.21

Splicing

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: chr17-73919597;