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GeneBe

11-92353483-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001367949.2(FAT3):c.1371G>A(p.Gln457=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0574 in 1,613,216 control chromosomes in the GnomAD database, including 3,275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.074 ( 579 hom., cov: 32)
Exomes 𝑓: 0.056 ( 2696 hom. )

Consequence

FAT3
NM_001367949.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.330
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-92353483-G-A is Benign according to our data. Variant chr11-92353483-G-A is described in ClinVar as [Benign]. Clinvar id is 3056107.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.33 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FAT3NM_001367949.2 linkuse as main transcriptc.1371G>A p.Gln457= synonymous_variant 2/28 ENST00000525166.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FAT3ENST00000525166.6 linkuse as main transcriptc.1371G>A p.Gln457= synonymous_variant 2/285 NM_001367949.2 Q8TDW7-1
FAT3ENST00000409404.6 linkuse as main transcriptc.1371G>A p.Gln457= synonymous_variant 1/255 P1Q8TDW7-3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0745
AC:
11329
AN:
152042
Hom.:
576
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.140
Gnomad AMI
AF:
0.0231
Gnomad AMR
AF:
0.0513
Gnomad ASJ
AF:
0.0899
Gnomad EAS
AF:
0.000387
Gnomad SAS
AF:
0.00663
Gnomad FIN
AF:
0.0269
Gnomad MID
AF:
0.0601
Gnomad NFE
AF:
0.0580
Gnomad OTH
AF:
0.0655
GnomAD3 exomes
AF:
0.0455
AC:
11241
AN:
247038
Hom.:
423
AF XY:
0.0431
AC XY:
5774
AN XY:
133944
show subpopulations
Gnomad AFR exome
AF:
0.142
Gnomad AMR exome
AF:
0.0300
Gnomad ASJ exome
AF:
0.0862
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00830
Gnomad FIN exome
AF:
0.0271
Gnomad NFE exome
AF:
0.0542
Gnomad OTH exome
AF:
0.0484
GnomAD4 exome
AF:
0.0557
AC:
81315
AN:
1461056
Hom.:
2696
Cov.:
32
AF XY:
0.0537
AC XY:
39036
AN XY:
726728
show subpopulations
Gnomad4 AFR exome
AF:
0.146
Gnomad4 AMR exome
AF:
0.0317
Gnomad4 ASJ exome
AF:
0.0895
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00935
Gnomad4 FIN exome
AF:
0.0274
Gnomad4 NFE exome
AF:
0.0600
Gnomad4 OTH exome
AF:
0.0555
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0744
AC:
11328
AN:
152160
Hom.:
579
Cov.:
32
AF XY:
0.0720
AC XY:
5352
AN XY:
74380
show subpopulations
Gnomad4 AFR
AF:
0.140
Gnomad4 AMR
AF:
0.0511
Gnomad4 ASJ
AF:
0.0899
Gnomad4 EAS
AF:
0.000388
Gnomad4 SAS
AF:
0.00663
Gnomad4 FIN
AF:
0.0269
Gnomad4 NFE
AF:
0.0580
Gnomad4 OTH
AF:
0.0648
Alfa
AF:
0.0665
Hom.:
316
Bravo
AF:
0.0795
Asia WGS
AF:
0.0130
AC:
46
AN:
3478

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 submitterclinical testingPreventionGenetics, part of Exact SciencesDec 09, 2019This 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
BayesDel_noAF
Benign
-0.60
Cadd
Benign
0.39
Dann
Benign
0.41

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.

Other links and lift over

dbSNP: rs10830903; hg19: chr11-92086649; API