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GeneBe

11-92353306-A-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001367949.2(FAT3):c.1194A>C(p.Val398=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,613,680 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00090 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0010 ( 1 hom. )

Consequence

FAT3
NM_001367949.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0330
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 Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
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=-0.73).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-92353306-A-C is Benign according to our data. Variant chr11-92353306-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3052770.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=-0.033 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FAT3NM_001367949.2 linkuse as main transcriptc.1194A>C p.Val398= synonymous_variant 2/28 ENST00000525166.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FAT3ENST00000525166.6 linkuse as main transcriptc.1194A>C p.Val398= synonymous_variant 2/285 NM_001367949.2 Q8TDW7-1
FAT3ENST00000409404.6 linkuse as main transcriptc.1194A>C p.Val398= synonymous_variant 1/255 P1Q8TDW7-3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000900
AC:
137
AN:
152198
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00275
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.00116
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000778
AC:
193
AN:
247924
Hom.:
0
AF XY:
0.000781
AC XY:
105
AN XY:
134492
show subpopulations
Gnomad AFR exome
AF:
0.000324
Gnomad AMR exome
AF:
0.00105
Gnomad ASJ exome
AF:
0.0000998
Gnomad EAS exome
AF:
0.0000557
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000140
Gnomad NFE exome
AF:
0.00127
Gnomad OTH exome
AF:
0.000833
GnomAD4 exome
AF:
0.00104
AC:
1517
AN:
1461364
Hom.:
1
Cov.:
31
AF XY:
0.000984
AC XY:
715
AN XY:
726940
show subpopulations
Gnomad4 AFR exome
AF:
0.000120
Gnomad4 AMR exome
AF:
0.000807
Gnomad4 ASJ exome
AF:
0.000115
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.000169
Gnomad4 NFE exome
AF:
0.00127
Gnomad4 OTH exome
AF:
0.000845
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000899
AC:
137
AN:
152316
Hom.:
0
Cov.:
32
AF XY:
0.000792
AC XY:
59
AN XY:
74480
show subpopulations
Gnomad4 AFR
AF:
0.000241
Gnomad4 AMR
AF:
0.00274
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00116
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000777
Hom.:
0
Bravo
AF:
0.000888
EpiCase
AF:
0.00120
EpiControl
AF:
0.00149

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

FAT3-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesDec 18, 2019This variant is classified as likely 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
-0.73
Cadd
Benign
1.2
Dann
Benign
0.53

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: rs139731877; hg19: chr11-92086472; API