16-87360308-G-T

Variant names:

• chr16-87360308-G-T
• NM_024735.5:c.399C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024735.5(FBXO31):​c.399C>A​(p.Asp133Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FBXO31 NM_024735.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709

Genes affected

FBXO31 (HGNC:16510): (F-box protein 31) This gene is a member of the F-box family. Members are classified into three classes according to the substrate interaction domain, FBW for WD40 repeats, FBL for leucing-rich repeats, and FBXO for other domains. This protein, classified into the last category because of the lack of a recognizable substrate binding domain, has been proposed to be a component of the SCF ubiquitination complex. It is thought to bind and recruit substrate for ubiquitination and degradation. This protein may have a role in regulating the cell cycle as well as dendrite growth and neuronal migration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29788154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO31	NM_024735.5	c.399C>A	p.Asp133Glu	missense_variant	Exon 2 of 9	ENST00000311635.12	NP_079011.3
FBXO31	NM_001282683.2	c.-118C>A		5_prime_UTR_variant	Exon 3 of 10		NP_001269612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO31	ENST00000311635.12	c.399C>A	p.Asp133Glu	missense_variant	Exon 2 of 9	1	NM_024735.5	ENSP00000310841.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461770 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727180

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.0025	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	4.4
DANN	Benign	0.97
DEOGEN2	Benign	0.064	T;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.84	T;D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	-0.16	N;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.6	N;.
REVEL	Uncertain	0.44
Sift	Benign	0.23	T;.
Sift4G	Benign	0.17	T;.
Polyphen		1.0	D;.
Vest4		0.46
MutPred		0.41		Loss of MoRF binding (P = 0.1552);Loss of MoRF binding (P = 0.1552);
MVP		0.79
MPC		1.0
ClinPred		0.69	D
GERP RS		-5.7
Varity_R		0.30
gMVP		0.48

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-87393914;