17-38962848-A-C

Position:

• chr17-38962848-A-C

Variant summary

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

The ENST00000378079.3(FBXO47):​c.178T>G​(p.Ser60Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FBXO47 ENST00000378079.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.814

Genes affected

FBXO47 (HGNC:31969): (F-box protein 47)

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=0.19239366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXO47	NM_001008777.3	c.178T>G	p.Ser60Ala	missense_variant	2/11	ENST00000378079.3	NP_001008777.2
FBXO47	XM_011524865.3	c.178T>G	p.Ser60Ala	missense_variant	2/11		XP_011523167.1
FBXO47	XM_011524866.4	c.178T>G	p.Ser60Ala	missense_variant	2/10		XP_011523168.1
FBXO47	XM_011524867.3	c.178T>G	p.Ser60Ala	missense_variant	2/10		XP_011523169.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBXO47	ENST00000378079.3	c.178T>G	p.Ser60Ala	missense_variant	2/11	1	NM_001008777.3	ENSP00000367319	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1456622 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 724870

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: 0.00

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

Mar 11, 2024

The c.178T>G (p.S60A) alteration is located in exon 2 (coding exon 1) of the FBXO47 gene. This alteration results from a T to G substitution at nucleotide position 178, causing the serine (S) at amino acid position 60 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	0.11
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.093	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	0.90	N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.029
Sift	Benign	0.20	T
Sift4G	Benign	0.36	T
Polyphen		0.090	B
Vest4		0.49
MutPred		0.37		Gain of relative solvent accessibility (P = 0.0215);
MVP		0.29
MPC		0.091
ClinPred		0.28	T
GERP RS		2.7
Varity_R		0.22
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr17-37119101;