chr7-102878356-C-A

Variant names:

• chr7-102878356-C-A
• rs751465472
• ENST00000440067.4:c.1753G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000440067.4(FBXL13):​c.1753G>T​(p.Ala585Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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. A585T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FBXL13 ENST00000440067.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 0 publications found

Genes affected

FBXL13 (HGNC:21658): (F-box and leucine rich repeat protein 13) Members of the F-box protein family, such as FBXL13, 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06736535).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBXL13	NM_001394494.2	c.1753G>T	p.Ala585Ser	missense_variant	Exon 16 of 21		NP_001381423.1
FBXL13	NM_145032.3	c.1483G>T	p.Ala495Ser	missense_variant	Exon 15 of 20		NP_659469.3
FBXL13	NM_001287150.2	c.1483G>T	p.Ala495Ser	missense_variant	Exon 15 of 19		NP_001274079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBXL13	ENST00000440067.4	c.1753G>T	p.Ala585Ser	missense_variant	Exon 16 of 21	3		ENSP00000390126.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454696 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 723496

African (AFR) AF: 0.00 AC: 0 AN: 33160

American (AMR) AF: 0.00 AC: 0 AN: 43706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26032

East Asian (EAS) AF: 0.00 AC: 0 AN: 39240

South Asian (SAS) AF: 0.00 AC: 0 AN: 84862

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53166

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108664

Other (OTH) AF: 0.00 AC: 0 AN: 60112

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.020
DANN	Benign	0.44
DEOGEN2	Benign	0.0029	.;T;T;.;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.43	T;.;T;T;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.067	T;T;T;T;T
MetaSVM	Benign	-0.93	T
PhyloP100		-1.2
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.2	N;N;N;.;N
REVEL	Benign	0.018
Sift	Benign	0.62	T;T;T;.;T
Sift4G	Benign	0.59	T;T;T;T;T
Polyphen		0.0030	B;B;B;.;B
Vest4		0.30
MutPred		0.41		Gain of disorder (P = 0.0088);Gain of disorder (P = 0.0088);Gain of disorder (P = 0.0088);.;Gain of disorder (P = 0.0088);
MVP		0.085
MPC		0.086
ClinPred		0.030	T
GERP RS		-4.3
Varity_R		0.043
gMVP		0.22
Mutation Taster		=94/6	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: rs751465472; hg19: chr7-102518803;