chr17-38945127-T-A

Variant names:

• chr17-38945127-T-A
• rs9906595
• NM_001008777.3:c.626A>T

Variant summary

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

The NM_001008777.3(FBXO47):​c.626A>T​(p.Gln209Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. Q209R) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FBXO47 NM_001008777.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10
• Publications: 32 publications found

Genes affected

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

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=0.08536905).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008777.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO47	NM_001008777.3	MANE Select	c.626A>T	p.Gln209Leu	missense	Exon 7 of 11	NP_001008777.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO47	ENST00000378079.3	TSL:1 MANE Select	c.626A>T	p.Gln209Leu	missense	Exon 7 of 11	ENSP00000367319.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458880 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725748

African (AFR) AF: 0.00 AC: 0 AN: 33428

American (AMR) AF: 0.00 AC: 0 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 86120

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109518

Other (OTH) AF: 0.00 AC: 0 AN: 60276

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Benign	0.68
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.52
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.1
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.020
Sift	Benign	0.81	T
Sift4G	Benign	0.30	T
Polyphen		0.0010	B
Vest4		0.25
MutPred		0.24		Loss of disorder (P = 0.0345)
MVP		0.22
MPC		0.068
ClinPred		0.055	T
GERP RS		3.5
Varity_R		0.062
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9906595; hg19: chr17-37101380;