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GeneBe

11-92352457-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001367949.2(FAT3):c.345C>T(p.Ala115=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00421 in 1,612,444 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0043 ( 20 hom. )

Consequence

FAT3
NM_001367949.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.560
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=-0.4).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-92352457-C-T is Benign according to our data. Variant chr11-92352457-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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=0.56 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FAT3NM_001367949.2 linkuse as main transcriptc.345C>T p.Ala115= synonymous_variant 2/28 ENST00000525166.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FAT3ENST00000525166.6 linkuse as main transcriptc.345C>T p.Ala115= synonymous_variant 2/285 NM_001367949.2 Q8TDW7-1
FAT3ENST00000409404.6 linkuse as main transcriptc.345C>T p.Ala115= synonymous_variant 1/255 P1Q8TDW7-3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00323
AC:
491
AN:
152082
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00106
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00773
Gnomad ASJ
AF:
0.00202
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000283
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00445
Gnomad OTH
AF:
0.00765
GnomAD3 exomes
AF:
0.00278
AC:
692
AN:
248612
Hom.:
2
AF XY:
0.00276
AC XY:
372
AN XY:
134884
show subpopulations
Gnomad AFR exome
AF:
0.000905
Gnomad AMR exome
AF:
0.00434
Gnomad ASJ exome
AF:
0.000995
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000139
Gnomad NFE exome
AF:
0.00431
Gnomad OTH exome
AF:
0.00515
GnomAD4 exome
AF:
0.00431
AC:
6293
AN:
1460244
Hom.:
20
Cov.:
31
AF XY:
0.00412
AC XY:
2996
AN XY:
726424
show subpopulations
Gnomad4 AFR exome
AF:
0.00111
Gnomad4 AMR exome
AF:
0.00504
Gnomad4 ASJ exome
AF:
0.00130
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000281
Gnomad4 NFE exome
AF:
0.00513
Gnomad4 OTH exome
AF:
0.00471
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00323
AC:
491
AN:
152200
Hom.:
2
Cov.:
32
AF XY:
0.00318
AC XY:
237
AN XY:
74432
show subpopulations
Gnomad4 AFR
AF:
0.00106
Gnomad4 AMR
AF:
0.00772
Gnomad4 ASJ
AF:
0.00202
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000283
Gnomad4 NFE
AF:
0.00446
Gnomad4 OTH
AF:
0.00757
Alfa
AF:
0.00398
Hom.:
0
Bravo
AF:
0.00400
EpiCase
AF:
0.00338
EpiControl
AF:
0.00528

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

FAT3-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJul 16, 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). -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMar 01, 2023FAT3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.40
Cadd
Benign
11
Dann
Benign
0.55

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs76685441; hg19: chr11-92085623; COSMIC: COSV53183764; COSMIC: COSV53183764; API