Variant 11-92353347-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001367949.2(FAT3):c.1235C>T(p.Ser412Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.058 in 1,613,420 control chromosomes in the GnomAD database, including 3,418 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 Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.078 ( 655 hom., cov: 32)

Exomes 𝑓: 0.056 ( 2763 hom. )

Consequence

FAT3
NM_001367949.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.16

Variant links:

Genes affected

FAT3 (HGNC:23112): (FAT atypical cadherin 3) Predicted to enable calcium ion binding activity. Predicted to be involved in cell-cell adhesion. Predicted to act upstream of or within several processes, including negative regulation of dendrite development; neuron migration; and retina layer formation. Predicted to be located in dendrite and plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

FAT3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023308992).

BP6

Variant 11-92353347-C-T is Benign according to our data. Variant chr11-92353347-C-T is described in ClinVar as [Benign]. Clinvar id is 3055330.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAT3	NM_001367949.2 linkuse as main transcript	c.1235C>T	p.Ser412Phe	missense_variant	2/28	ENST00000525166.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAT3	ENST00000525166.6 linkuse as main transcript	c.1235C>T	p.Ser412Phe	missense_variant	2/28	5	NM_001367949.2		Q8TDW7-1
FAT3	ENST00000409404.6 linkuse as main transcript	c.1235C>T	p.Ser412Phe	missense_variant	1/25	5		P1	Q8TDW7-3

Frequencies

GnomAD3 genomes

AF:

0.0777

AC:

11823

AN:

152132

Hom.:

652

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0531

Gnomad ASJ

AF:

0.0894

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00663

Gnomad FIN

AF:

0.0268

Gnomad MID

AF:

0.0605

Gnomad NFE

AF:

0.0580

Gnomad OTH

AF:

0.0674

GnomAD3 exomes

AF:

0.0462

AC:

11416

AN:

247230

Hom.:

446

AF XY:

0.0436

AC XY:

5850

AN XY:

134168

show subpopulations

Gnomad AFR exome

AF:

0.153

Gnomad AMR exome

AF:

0.0305

Gnomad ASJ exome

AF:

0.0859

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00833

Gnomad FIN exome

AF:

0.0270

Gnomad NFE exome

AF:

0.0540

Gnomad OTH exome

AF:

0.0490

GnomAD4 exome

AF:

0.0560

AC:

81782

AN:

1461170

Hom.:

2763

Cov.:

AF XY:

0.0540

AC XY:

39229

AN XY:

726826

show subpopulations

Gnomad4 AFR exome

AF:

0.158

Gnomad4 AMR exome

AF:

0.0323

Gnomad4 ASJ exome

AF:

0.0895

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00936

Gnomad4 FIN exome

AF:

0.0274

Gnomad4 NFE exome

AF:

0.0600

Gnomad4 OTH exome

AF:

0.0561

GnomAD4 genome

AF:

0.0776

AC:

11822

AN:

152250

Hom.:

655

Cov.:

AF XY:

0.0748

AC XY:

5569

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.151

Gnomad4 AMR

AF:

0.0529

Gnomad4 ASJ

AF:

0.0894

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00663

Gnomad4 FIN

AF:

0.0268

Gnomad4 NFE

AF:

0.0580

Gnomad4 OTH

AF:

0.0667

Alfa

AF:

0.0613

Hom.:

772

Bravo

AF:

0.0831

TwinsUK

AF:

0.0591

AC:

219

ALSPAC

AF:

0.0576

AC:

222

ESP6500AA

AF:

0.138

AC:

511

ESP6500EA

AF:

0.0557

AC:

457

ExAC

AF:

0.0461

AC:

5566

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0568

EpiControl

AF:

0.0588

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

FAT3-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 09, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.44

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.10

FATHMM_MKL

Benign

0.57

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.089

Sift

Benign

0.035

D;D

Vest4

0.52

ClinPred

0.0051

GERP RS

4.7

Varity_R

0.096

gMVP

0.38

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

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