chr1-16251299-C-T

Variant names:

• chr1-16251299-C-T
• rs35196193
• NM_018994.3:c.1525G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018994.3(FBXO42):​c.1525G>A​(p.Ala509Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0644 in 1,614,138 control chromosomes in the GnomAD database, including 3,637 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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: 𝑓 0.049 (235 hom., cov: 32)
  • Exomes 𝑓: 0.066 (3402 hom.)
• Consequence: FBXO42 NM_018994.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.509

Genes affected

FBXO42 (HGNC:29249): (F-box protein 42) Members of the F-box protein family, such as FBXO42, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (SKP1A; MIM 601434), cullin (see CUL1; MIM 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015014708).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO42	NM_018994.3	c.1525G>A	p.Ala509Thr	missense_variant	Exon 10 of 10	ENST00000375592.8	NP_061867.1
FBXO42	XM_047422747.1	c.1525G>A	p.Ala509Thr	missense_variant	Exon 12 of 12		XP_047278703.1
FBXO42	XM_047422750.1	c.1525G>A	p.Ala509Thr	missense_variant	Exon 12 of 12		XP_047278706.1
FBXO42	XM_047422751.1	c.1525G>A	p.Ala509Thr	missense_variant	Exon 12 of 12		XP_047278707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO42	ENST00000375592.8	c.1525G>A	p.Ala509Thr	missense_variant	Exon 10 of 10	1	NM_018994.3	ENSP00000364742.3
FBXO42	ENST00000444116.1	c.679G>A	p.Ala227Thr	missense_variant	Exon 4 of 4	5		ENSP00000412416.1
FBXO42	ENST00000456164.5	c.679G>A	p.Ala227Thr	missense_variant	Exon 3 of 3	2		ENSP00000415663.1

Frequencies

GnomAD3 genomes AF: 0.0489 AC: 7435 AN: 152160 Hom.: 235 Cov.: 32

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0409

Gnomad ASJ AF: 0.0723

Gnomad EAS AF: 0.0303

Gnomad SAS AF: 0.0709

Gnomad FIN AF: 0.0412

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0687

Gnomad OTH AF: 0.0478

GnomAD3 exomes AF: 0.0550 AC: 13824 AN: 251458 Hom.: 485 AF XY: 0.0582 AC XY: 7916 AN XY: 135904

Gnomad AFR exome AF: 0.0193

Gnomad AMR exome AF: 0.0227

Gnomad ASJ exome AF: 0.0687

Gnomad EAS exome AF: 0.0310

Gnomad SAS exome AF: 0.0742

Gnomad FIN exome AF: 0.0449

Gnomad NFE exome AF: 0.0692

Gnomad OTH exome AF: 0.0572

GnomAD4 exome AF: 0.0660 AC: 96555 AN: 1461860 Hom.: 3402 Cov.: 31 AF XY: 0.0664 AC XY: 48285 AN XY: 727234

Gnomad4 AFR exome AF: 0.0180

Gnomad4 AMR exome AF: 0.0243

Gnomad4 ASJ exome AF: 0.0716

Gnomad4 EAS exome AF: 0.0229

Gnomad4 SAS exome AF: 0.0739

Gnomad4 FIN exome AF: 0.0439

Gnomad4 NFE exome AF: 0.0716

Gnomad4 OTH exome AF: 0.0594

GnomAD4 genome AF: 0.0488 AC: 7437 AN: 152278 Hom.: 235 Cov.: 32 AF XY: 0.0481 AC XY: 3581 AN XY: 74462

Gnomad4 AFR AF: 0.0197

Gnomad4 AMR AF: 0.0408

Gnomad4 ASJ AF: 0.0723

Gnomad4 EAS AF: 0.0303

Gnomad4 SAS AF: 0.0715

Gnomad4 FIN AF: 0.0412

Gnomad4 NFE AF: 0.0687

Gnomad4 OTH AF: 0.0473

Alfa AF: 0.0657 Hom.: 551

Bravo AF: 0.0466

TwinsUK AF: 0.0755 AC: 280

ALSPAC AF: 0.0675 AC: 260

ESP6500AA AF: 0.0211 AC: 93

ESP6500EA AF: 0.0679 AC: 584

ExAC AF: 0.0557 AC: 6759

Asia WGS AF: 0.0520 AC: 180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.50
DANN	Benign	0.79
DEOGEN2	Benign	0.018	T;T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.59	T;.;T
MetaRNN	Benign	0.0015	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.59	N;N;N
REVEL	Benign	0.016
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.58	T;.;.
Polyphen		0.0	B;.;.
Vest4		0.011
MPC		0.25
ClinPred		0.000013	T
GERP RS		-5.0
Varity_R		0.020
gMVP		0.17

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: rs35196193; hg19: chr1-16577794;