rs2077330490

Variant names:

• chr2-229996888-G-C
• rs2077330490
• NM_174899.5:c.343G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-229996888-G-C
• chr2-229996888-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_174899.5(FBXO36):​c.343G>C​(p.Ala115Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A115S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FBXO36 NM_174899.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.65
• Publications: 0 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.865

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXO36	NM_174899.5	c.343G>C	p.Ala115Pro	missense_variant	Exon 3 of 4	ENST00000283946.8	NP_777559.3
FBXO36	XM_005246317.3	c.268G>C	p.Ala90Pro	missense_variant	Exon 3 of 4		XP_005246374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXO36	ENST00000283946.8	c.343G>C	p.Ala115Pro	missense_variant	Exon 3 of 4	1	NM_174899.5	ENSP00000283946.3
FBXO36	ENST00000373652.7	c.250G>C	p.Ala84Pro	missense_variant	Exon 4 of 5	1		ENSP00000362756.3
FBXO36	ENST00000409992.1	c.283G>C	p.Ala95Pro	missense_variant	Exon 3 of 4	5		ENSP00000386673.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.086	.;T;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.80	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Pathogenic	0.87	D;D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	.;M;.
PhyloP100		3.6
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.4	N;N;N
REVEL	Benign	0.26
Sift	Benign	0.068	T;T;T
Sift4G	Uncertain	0.055	T;T;T
Polyphen		0.96	.;D;.
Vest4		0.87
MutPred		0.71		.;Gain of relative solvent accessibility (P = 0.0215);.;
MVP		0.52
MPC		0.34
ClinPred		0.96	D
GERP RS		4.5
Varity_R		0.63
gMVP		0.66
Mutation Taster		=53/47	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: rs2077330490; hg19: chr2-230861604;