NM_001394494.2:c.1951G>C

Variant names:

• chr7-102854815-C-G
• rs781733633
• NM_001394494.2:c.1951G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001394494.2(FBXL13):​c.1951G>C​(p.Val651Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000486 in 1,439,546 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: FBXL13 NM_001394494.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.184
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058544695).
• BP6: Variant 7-102854815-C-G is Benign according to our data. Variant chr7-102854815-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2492878.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394494.2. 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
	FBXL13	NM_001394494.2	MANE Select	c.1951G>C	p.Val651Leu	missense	Exon 18 of 21	NP_001381423.1	C9JI88
	FBXL13	NM_145032.3		c.1681G>C	p.Val561Leu	missense	Exon 17 of 20	NP_659469.3	Q8N1P0
	FBXL13	NM_001111038.2		c.1681G>C	p.Val561Leu	missense	Exon 17 of 19	NP_001104508.1	Q8NEE6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBXL13	ENST00000440067.4	TSL:3 MANE Select	c.1951G>C	p.Val651Leu	missense	Exon 18 of 21	ENSP00000390126.2	C9JI88
	FBXL13	ENST00000448002.6	TSL:1	n.1951G>C		non_coding_transcript_exon	Exon 18 of 21	ENSP00000405434.2	E7ERH8
	FBXL13	ENST00000455112.7	TSL:1	n.*1680G>C		non_coding_transcript_exon	Exon 17 of 19	ENSP00000391550.3	A0A8V8NC12

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000409 AC: 1 AN: 244648 AF XY: 0.00000754

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: 0.00000895

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000486 AC: 7 AN: 1439546 Hom.: 0 Cov.: 26 AF XY: 0.00000419 AC XY: 3 AN XY: 716578

African (AFR) AF: 0.00 AC: 0 AN: 32832

American (AMR) AF: 0.00 AC: 0 AN: 42684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25774

East Asian (EAS) AF: 0.00 AC: 0 AN: 39134

South Asian (SAS) AF: 0.00 AC: 0 AN: 82798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52942

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5660

European-Non Finnish (NFE) AF: 0.00000546 AC: 6 AN: 1098196

Other (OTH) AF: 0.0000168 AC: 1 AN: 59526

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000825 AC: 1

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	2.1
DANN	Benign	0.64
DEOGEN2	Benign	0.00018	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.92	T
PhyloP100		-0.18
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.23	N
REVEL	Benign	0.017
Sift	Benign	1.0	T
Sift4G	Benign	0.98	T
Polyphen		0.0010	B
Vest4		0.068
MutPred		0.41		Gain of disorder (P = 0.1522)
MVP		0.13
MPC		0.091
ClinPred		0.010	T
GERP RS		-3.5
Varity_R		0.048
gMVP		0.22
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs781733633; hg19: chr7-102495262;