chr16-87334218-G-A

Variant names:

• chr16-87334218-G-A
• rs61115074
• NM_024735.5:c.1065C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_024735.5(FBXO31):​c.1065C>T​(p.Pro355Pro) 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:3
• Conservation: PhyloP100: -2.51
• Publications: 2 publications found

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]

FBXO31 Gene-Disease associations (from GenCC):

• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• cerebral palsy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• intellectual disability, autosomal recessive

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• intellectual disability, autosomal recessive 45

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000131152 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 24 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024735.5. 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
	FBXO31	NM_024735.5	MANE Select	c.1065C>T	p.Pro355Pro	synonymous	Exon 8 of 9	NP_079011.3
	FBXO31	NM_001282683.2		c.549C>T	p.Pro183Pro	synonymous	Exon 9 of 10	NP_001269612.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO31	ENST00000311635.12	TSL:1 MANE Select	c.1065C>T	p.Pro355Pro	synonymous	Exon 8 of 9	ENSP00000310841.4
	ENSG00000131152	ENST00000568879.1	TSL:4	c.54C>T	p.Pro18Pro	synonymous	Exon 1 of 5	ENSP00000454386.1
	FBXO31	ENST00000636077.2	TSL:5	c.1152C>T	p.Pro384Pro	synonymous	Exon 9 of 10	ENSP00000490402.2

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

GnomAD2 exomes AF: 0.00231 AC: 574 AN: 248388 AF XY: 0.00174

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 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

African (AFR) AF: 0.0335 AC: 1120 AN: 33422

American (AMR) AF: 0.00157 AC: 70 AN: 44578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26042

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39674

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86034

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52512

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5758

European-Non Finnish (NFE) AF: 0.0000297 AC: 33 AN: 1111192

Other (OTH) AF: 0.00252 AC: 152 AN: 60302

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

African (AFR) AF: 0.0323 AC: 1345 AN: 41582

American (AMR) AF: 0.00307 AC: 47 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68016

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

Jan 19, 2017

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.11
DANN	Benign	0.69
PhyloP100		-2.5
PromoterAI		0.0084	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs61115074; hg19: chr16-87367824;