16-87331044-T-C

Variant names:

• chr16-87331044-T-C
• rs1062746
• NM_024735.5:c.*244A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024735.5(FBXO31):​c.*244A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 492,278 control chromosomes in the GnomAD database, including 33,863 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (10245 hom., cov: 32)
  • Exomes 𝑓: 0.35 (23618 hom.)
• Consequence: FBXO31 NM_024735.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440
• Publications: 15 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO31	NM_024735.5	c.*244A>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000311635.12	NP_079011.3
FBXO31	NM_001282683.2	c.*244A>G		3_prime_UTR_variant	Exon 10 of 10		NP_001269612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO31	ENST00000311635.12	c.*244A>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_024735.5	ENSP00000310841.4
ENSG00000131152	ENST00000568879.1	c.386+2842A>G		intron_variant	Intron 1 of 4	4		ENSP00000454386.1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53893 AN: 151992 Hom.: 10244 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.360

GnomAD4 exome AF: 0.351 AC: 119397 AN: 340168 Hom.: 23618 Cov.: 3 AF XY: 0.340 AC XY: 60389 AN XY: 177704

African (AFR) AF: 0.294 AC: 2981 AN: 10146

American (AMR) AF: 0.313 AC: 4514 AN: 14402

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 3828 AN: 10820

East Asian (EAS) AF: 0.121 AC: 2735 AN: 22604

South Asian (SAS) AF: 0.135 AC: 5060 AN: 37480

European-Finnish (FIN) AF: 0.308 AC: 6387 AN: 20766

Middle Eastern (MID) AF: 0.311 AC: 478 AN: 1536

European-Non Finnish (NFE) AF: 0.426 AC: 86455 AN: 202726

Other (OTH) AF: 0.353 AC: 6959 AN: 19688

GnomAD4 genome AF: 0.354 AC: 53911 AN: 152110 Hom.: 10245 Cov.: 32 AF XY: 0.342 AC XY: 25390 AN XY: 74348

African (AFR) AF: 0.302 AC: 12540 AN: 41468

American (AMR) AF: 0.344 AC: 5262 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1241 AN: 3468

East Asian (EAS) AF: 0.117 AC: 606 AN: 5172

South Asian (SAS) AF: 0.118 AC: 568 AN: 4820

European-Finnish (FIN) AF: 0.295 AC: 3122 AN: 10576

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29408 AN: 67996

Other (OTH) AF: 0.357 AC: 753 AN: 2108

Alfa AF: 0.411 Hom.: 15177

Bravo AF: 0.356

Asia WGS AF: 0.131 AC: 460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.45
PhyloP100		-0.044
Mutation Taster		=100/0	polymorphism (auto)

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: rs1062746; hg19: chr16-87364650;