chr11-92886994-A-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001367949.2(FAT3):​c.12938-6A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000486 in 1,441,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

FAT3
NM_001367949.2 splice_region, intron

Scores

2
Splicing: ADA: 0.00005853
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.128

Publications

0 publications found
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAT3NM_001367949.2 linkc.12938-6A>C splice_region_variant, intron_variant Intron 24 of 27 ENST00000525166.6 NP_001354878.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAT3ENST00000525166.6 linkc.12938-6A>C splice_region_variant, intron_variant Intron 24 of 27 5 NM_001367949.2 ENSP00000432586.2 Q8TDW7-1E9PQ73

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000486
AC:
7
AN:
1441266
Hom.:
0
Cov.:
30
AF XY:
0.00000140
AC XY:
1
AN XY:
714656
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33248
American (AMR)
AF:
0.00
AC:
0
AN:
41226
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25688
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39248
South Asian (SAS)
AF:
0.0000121
AC:
1
AN:
82452
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52414
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5750
European-Non Finnish (NFE)
AF:
0.00000545
AC:
6
AN:
1101462
Other (OTH)
AF:
0.00
AC:
0
AN:
59778
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.069
DANN
Benign
0.50
PhyloP100
-0.13

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000059
dbscSNV1_RF
Benign
0.026
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

Other links and lift over

dbSNP: rs12421052; hg19: chr11-92620160; API