2-229976295-C-T

Variant names:

• chr2-229976295-C-T
• rs61753284
• NM_174899.5:c.151C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_174899.5(FBXO36):​c.151C>T​(p.Pro51Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00586 in 1,613,518 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0048 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0060 (38 hom.)
• Consequence: FBXO36 NM_174899.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.81
• Publications: 11 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0110967755).
• BP6: Variant 2-229976295-C-T is Benign according to our data. Variant chr2-229976295-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2651989.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00598 (8738/1461308) while in subpopulation MID AF = 0.0255 (147/5766). AF 95% confidence interval is 0.0221. There are 38 homozygotes in GnomAdExome4. There are 4343 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174899.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO36	NM_174899.5	MANE Select	c.151C>T	p.Pro51Ser	missense	Exon 2 of 4	NP_777559.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXO36	ENST00000283946.8	TSL:1 MANE Select	c.151C>T	p.Pro51Ser	missense	Exon 2 of 4	ENSP00000283946.3	Q8NEA4-1
	FBXO36	ENST00000373652.7	TSL:1	c.58C>T	p.Pro20Ser	missense	Exon 3 of 5	ENSP00000362756.3	Q8NEA4-3
	FBXO36	ENST00000465090.2	TSL:1	n.174C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.00477 AC: 725 AN: 152092 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.00413

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00728

Gnomad OTH AF: 0.00958

GnomAD2 exomes AF: 0.00489 AC: 1229 AN: 251162 AF XY: 0.00506

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00463

Gnomad ASJ exome AF: 0.00993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000878

Gnomad NFE exome AF: 0.00714

Gnomad OTH exome AF: 0.00686

GnomAD4 exome AF: 0.00598 AC: 8738 AN: 1461308 Hom.: 38 Cov.: 30 AF XY: 0.00597 AC XY: 4343 AN XY: 726952

African (AFR) AF: 0.00167 AC: 56 AN: 33462

American (AMR) AF: 0.00450 AC: 201 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00923 AC: 241 AN: 26124

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39618

South Asian (SAS) AF: 0.00276 AC: 238 AN: 86224

European-Finnish (FIN) AF: 0.00124 AC: 66 AN: 53404

Middle Eastern (MID) AF: 0.0255 AC: 147 AN: 5766

European-Non Finnish (NFE) AF: 0.00670 AC: 7451 AN: 1111636

Other (OTH) AF: 0.00558 AC: 337 AN: 60370

GnomAD4 genome AF: 0.00476 AC: 724 AN: 152210 Hom.: 5 Cov.: 32 AF XY: 0.00437 AC XY: 325 AN XY: 74432

African (AFR) AF: 0.00116 AC: 48 AN: 41542

American (AMR) AF: 0.00412 AC: 63 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4828

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10594

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00728 AC: 495 AN: 68000

Other (OTH) AF: 0.00900 AC: 19 AN: 2110

Alfa AF: 0.00659 Hom.: 2

Bravo AF: 0.00496

TwinsUK AF: 0.00458 AC: 17

ALSPAC AF: 0.00415 AC: 16

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00779 AC: 67

ExAC AF: 0.00476 AC: 578

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00911

EpiControl AF: 0.00853

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.35	T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.011	T
MetaSVM	Uncertain	0.40	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		4.8
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-6.9	D
REVEL	Uncertain	0.51
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.69
MVP		0.94
MPC		0.33
ClinPred		0.025	T
GERP RS		5.7
Varity_R		0.84
gMVP		0.77
Mutation Taster		=99/1	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: rs61753284; hg19: chr2-230841011; COSMIC: COSV99033477; COSMIC: COSV99033477;