Variant 11-92353292-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001367949.2(FAT3):c.1180G>A(p.Val394Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000967 in 1,613,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000099 ( 0 hom. )

Consequence

FAT3
NM_001367949.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.172

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.046567738).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAT3	NM_001367949.2 linkuse as main transcript	c.1180G>A	p.Val394Met	missense_variant	2/28	ENST00000525166.6	NP_001354878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAT3	ENST00000525166.6 linkuse as main transcript	c.1180G>A	p.Val394Met	missense_variant	2/28	5	NM_001367949.2	ENSP00000432586		Q8TDW7-1
FAT3	ENST00000409404.6 linkuse as main transcript	c.1180G>A	p.Val394Met	missense_variant	1/25	5		ENSP00000387040	P1	Q8TDW7-3

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000686

AC:

AN:

247964

Hom.:

AF XY:

0.0000669

AC XY:

AN XY:

134502

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000223

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000802

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000985

AC:

144

AN:

1461322

Hom.:

Cov.:

AF XY:

0.0000784

AC XY:

AN XY:

726904

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000113

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000170

Hom.:

Bravo

AF:

0.0000680

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.0000828

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000594

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

Jan 23, 2023

The c.1180G>A (p.V394M) alteration is located in exon 1 (coding exon 1) of the FAT3 gene. This alteration results from a G to A substitution at nucleotide position 1180, causing the valine (V) at amino acid position 394 to be replaced by a methionine (M). 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

-0.43

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.26

T;T

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.18

M_CAP

Benign

0.0081

MetaRNN

Benign

0.047

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

0.23

N;N

REVEL

Benign

0.032

Sift

Benign

0.24

T;T

Vest4

0.17

MVP

0.082

ClinPred

0.0042

GERP RS

1.4

Varity_R

0.031

gMVP

0.26

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