chr16-87383628-G-A

Variant names:

• chr16-87383628-G-A
• rs780050895
• NM_024735.5:c.117C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_024735.5(FBXO31):​c.117C>T​(p.Pro39Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000233 in 1,285,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P39P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: FBXO31 NM_024735.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 0 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

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP7: Synonymous conserved (PhyloP=-1.31 with no splicing effect.

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.117C>T	p.Pro39Pro	synonymous	Exon 1 of 9	NP_079011.3
	FBXO31	NM_001282683.2		c.-177+6109C>T		intron	N/A	NP_001269612.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO31	ENST00000311635.12	TSL:1 MANE Select	c.117C>T	p.Pro39Pro	synonymous	Exon 1 of 9	ENSP00000310841.4
	FBXO31	ENST00000636077.2	TSL:5	c.117C>T	p.Pro39Pro	synonymous	Exon 1 of 10	ENSP00000490402.2
	FBXO31	ENST00000971306.1		c.117C>T	p.Pro39Pro	synonymous	Exon 1 of 10	ENSP00000641365.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000523 AC: 3 AN: 57396 AF XY: 0.0000294

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000309

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000233 AC: 3 AN: 1285812 Hom.: 0 Cov.: 35 AF XY: 0.00000158 AC XY: 1 AN XY: 633600

African (AFR) AF: 0.00 AC: 0 AN: 25354

American (AMR) AF: 0.000148 AC: 3 AN: 20322

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21250

East Asian (EAS) AF: 0.00 AC: 0 AN: 27784

South Asian (SAS) AF: 0.00 AC: 0 AN: 67008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34664

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1032832

Other (OTH) AF: 0.00 AC: 0 AN: 52856

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	7.2
DANN	Benign	0.95
PhyloP100		-1.3
PromoterAI		0.016	Neutral

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: rs780050895; hg19: chr16-87417234;