16-87334218-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_024735.5(FBXO31):c.1065C>T(p.Pro355=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,611,846 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0092 (24 hom., cov: 34)
  • Exomes 𝑓: 0.00096 (22 hom.)
• Consequence: FBXO31 NM_024735.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.51

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-87334218-G-A is Benign according to our data. Variant chr16-87334218-G-A is described in ClinVar as [Benign]. Clinvar id is 435179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00925 (1409/152332) while in subpopulation AFR AF= 0.0323 (1345/41582). AF 95% confidence interval is 0.0309. There are 24 homozygotes in gnomad4. There are 667 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBXO31	NM_024735.5	c.1065C>T	p.Pro355=	synonymous_variant	8/9	ENST00000311635.12
FBXO31	NM_001282683.2	c.549C>T	p.Pro183=	synonymous_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBXO31	ENST00000311635.12	c.1065C>T	p.Pro355=	synonymous_variant	8/9	1	NM_024735.5	P1
FBXO31	ENST00000636077.2	c.1152C>T	p.Pro384=	synonymous_variant	9/10	5
FBXO31	ENST00000618298.6	c.549C>T	p.Pro183=	synonymous_variant	8/9	5
FBXO31	ENST00000565593.1	c.288-97C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00925 AC: 1408 AN: 152214 Hom.: 24 Cov.: 34

Gnomad AFR AF: 0.0324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00307

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.00231 AC: 574 AN: 248388 Hom.: 14 AF XY: 0.00174 AC XY: 234 AN XY: 134612

Gnomad AFR exome AF: 0.0326

Gnomad AMR exome AF: 0.00111

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000220

Gnomad SAS exome AF: 0.0000329

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000268

Gnomad OTH exome AF: 0.000497

GnomAD4 exome AF: 0.000958 AC: 1398 AN: 1459514 Hom.: 22 Cov.: 32 AF XY: 0.000824 AC XY: 598 AN XY: 726000

Gnomad4 AFR exome AF: 0.0335

Gnomad4 AMR exome AF: 0.00157

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.0000190

Gnomad4 NFE exome AF: 0.0000297

Gnomad4 OTH exome AF: 0.00252

GnomAD4 genome AF: 0.00925 AC: 1409 AN: 152332 Hom.: 24 Cov.: 34 AF XY: 0.00895 AC XY: 667 AN XY: 74486

Gnomad4 AFR AF: 0.0323

Gnomad4 AMR AF: 0.00307

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00457 Hom.: 2

Bravo AF: 0.0105

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 19, 2017

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.11
Dann	Benign	0.69

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

LitVar

Other links and lift over

dbSNP: rs61115074; hg19: chr16-87367824;