rs149438648

Variant names:

• chr2-230010743-C-A
• rs149438648
• NM_174899.5:c.426C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-230010743-C-A
• chr2-230010743-C-G
• chr2-230010743-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_174899.5(FBXO36):​c.426C>A​(p.Cys142*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FBXO36 NM_174899.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 1 publications found

Genes affected

FBXO36 (HGNC:27020): (F-box protein 36) Members of the F-box protein family, such as FBXO36, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (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, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO36	NM_174899.5	c.426C>A	p.Cys142*	stop_gained	Exon 4 of 4	ENST00000283946.8	NP_777559.3
FBXO36	XM_005246317.3	c.351C>A	p.Cys117*	stop_gained	Exon 4 of 4		XP_005246374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO36	ENST00000283946.8	c.426C>A	p.Cys142*	stop_gained	Exon 4 of 4	1	NM_174899.5	ENSP00000283946.3
FBXO36	ENST00000373652.7	c.333C>A	p.Cys111*	stop_gained	Exon 5 of 5	1		ENSP00000362756.3
FBXO36	ENST00000409992.1	c.366C>A	p.Cys122*	stop_gained	Exon 4 of 4	5		ENSP00000386673.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250764 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.000164

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461332 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726946

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111592

Other (OTH) AF: 0.0000166 AC: 1 AN: 60362

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Benign	22
DANN	Uncertain	0.98
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.11	N
PhyloP100		-1.5
Vest4		0.15
GERP RS		-2.0
Mutation Taster		=71/129	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs149438648; hg19: chr2-230875459;