7-102854839-G-A

Variant names:

• chr7-102854839-G-A
• rs777955993
• NM_001394494.2:c.1927C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394494.2(FBXL13):​c.1927C>T​(p.His643Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000631 in 1,585,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: FBXL13 NM_001394494.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.60
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18882).

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.1927C>T	p.His643Tyr	missense	Exon 18 of 21	NP_001381423.1	C9JI88
	FBXL13	NM_145032.3		c.1657C>T	p.His553Tyr	missense	Exon 17 of 20	NP_659469.3	Q8N1P0
	FBXL13	NM_001111038.2		c.1657C>T	p.His553Tyr	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.1927C>T	p.His643Tyr	missense	Exon 18 of 21	ENSP00000390126.2	C9JI88
	FBXL13	ENST00000448002.6	TSL:1	n.1927C>T		non_coding_transcript_exon	Exon 18 of 21	ENSP00000405434.2	E7ERH8
	FBXL13	ENST00000455112.7	TSL:1	n.*1656C>T		non_coding_transcript_exon	Exon 17 of 19	ENSP00000391550.3	A0A8V8NC12

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151958 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000967

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000824 AC: 2 AN: 242706 AF XY: 0.00000760

Gnomad AFR exome AF: 0.000127

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: 0.00

GnomAD4 exome AF: 0.00000419 AC: 6 AN: 1433238 Hom.: 0 Cov.: 26 AF XY: 0.00000560 AC XY: 4 AN XY: 713778

African (AFR) AF: 0.0000919 AC: 3 AN: 32638

American (AMR) AF: 0.00 AC: 0 AN: 42282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25646

East Asian (EAS) AF: 0.00 AC: 0 AN: 39054

South Asian (SAS) AF: 0.00 AC: 0 AN: 82226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52850

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5634

European-Non Finnish (NFE) AF: 0.00000274 AC: 3 AN: 1093636

Other (OTH) AF: 0.00 AC: 0 AN: 59272

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151958 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74222

African (AFR) AF: 0.0000967 AC: 4 AN: 41380

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67966

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.33
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.0082	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.6
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.12
Sift	Benign	0.10	T
Sift4G	Benign	0.62	T
Polyphen		0.56	P
Vest4		0.35
MutPred		0.42		Loss of disorder (P = 0.0398)
MVP		0.23
MPC		0.34
ClinPred		0.27	T
GERP RS		5.1
Varity_R		0.66
gMVP		0.44
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs777955993; hg19: chr7-102495286; COSMIC: COSV57544983; COSMIC: COSV57544983;