Variant 17-15619077-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006382.4(FBXW10B):c.436C>T(p.Pro146Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,613,782 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 4 hom. )

Consequence

FBXW10B
NM_006382.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.256

Variant links:

Genes affected

FBXW10B (HGNC:14379): (F-box and WD repeat domain containing 10B) Members of the F-box protein family, such as FBXW10, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603034), 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]

FBXW10B links:

ENSG00000251537 (HGNC:):

ENSG00000251537 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0070494413).

BS2

High Homozygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBXW10B	NM_006382.4 link	c.436C>T	p.Pro146Ser	missense_variant	1/12	ENST00000395906.8	NP_006373.2	O95170-1Q59EB2
FBXW10B	NM_001282540.2 link	c.436C>T	p.Pro146Ser	missense_variant	1/13		NP_001269469.1	Q9BXD7A0A087WSX6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FBXW10B	ENST00000395906.8 link	c.436C>T	p.Pro146Ser	missense_variant	1/12	1	NM_006382.4	ENSP00000379242.4	O95170-1
ENSG00000251537	ENST00000455584.2 link	c.1436-3268C>T		intron_variant		2		ENSP00000402644.2	H0Y626
FBXW10B	ENST00000395667.7 link	c.436C>T	p.Pro146Ser	missense_variant	1/13	5		ENSP00000379026.2	A0A087WSX6

Frequencies

GnomAD3 genomes

AF:

0.00135

AC:

205

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000556

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000578

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00221

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00116

AC:

289

AN:

250114

Hom.:

AF XY:

0.00119

AC XY:

161

AN XY:

135490

show subpopulations

Gnomad AFR exome

AF:

0.000637

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00143

Gnomad NFE exome

AF:

0.00202

Gnomad OTH exome

AF:

0.000659

GnomAD4 exome

AF:

0.00165

AC:

2411

AN:

1461668

Hom.:

Cov.:

AF XY:

0.00163

AC XY:

1183

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00142

Gnomad4 NFE exome

AF:

0.00201

Gnomad4 OTH exome

AF:

0.00114

GnomAD4 genome

AF:

0.00135

AC:

205

AN:

152114

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

105

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.000555

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000578

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.00221

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00239

Hom.:

Bravo

AF:

0.00103

ESP6500AA

AF:

0.000924

AC:

ESP6500EA

AF:

0.00177

AC:

ExAC

AF:

0.00103

AC:

125

EpiCase

AF:

0.00169

EpiControl

AF:

0.00207

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.436C>T (p.P146S) alteration is located in exon 1 (coding exon 1) of the CDRT1 gene. This alteration results from a C to T substitution at nucleotide position 436, causing the proline (P) at amino acid position 146 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.63

CADD

Benign

9.9

DANN

Benign

0.82

DEOGEN2

Benign

0.0070

.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.0070

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.83

.;L

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.11

Sift

Benign

0.59

T;T

Sift4G

Benign

0.33

T;T

Polyphen

0.010

.;B

Vest4

0.14

MVP

0.030

ClinPred

0.0023

GERP RS

0.23

Varity_R

0.034

gMVP

0.072

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over