NM_001367949.2:c.12938-6A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001367949.2(FAT3):​c.12938-6A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,593,294 control chromosomes in the GnomAD database, including 9,212 homozygotes. 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: 𝑓 0.086 ( 720 hom., cov: 33)
Exomes 𝑓: 0.11 ( 8492 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

10 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]

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAT3NM_001367949.2 linkc.12938-6A>T 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>T splice_region_variant, intron_variant Intron 24 of 27 5 NM_001367949.2 ENSP00000432586.2 Q8TDW7-1E9PQ73

Frequencies

GnomAD3 genomes
AF:
0.0856
AC:
13031
AN:
152168
Hom.:
716
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0208
Gnomad AMI
AF:
0.00768
Gnomad AMR
AF:
0.127
Gnomad ASJ
AF:
0.0988
Gnomad EAS
AF:
0.137
Gnomad SAS
AF:
0.120
Gnomad FIN
AF:
0.148
Gnomad MID
AF:
0.0665
Gnomad NFE
AF:
0.100
Gnomad OTH
AF:
0.0775
GnomAD2 exomes
AF:
0.115
AC:
25159
AN:
218650
AF XY:
0.114
show subpopulations
Gnomad AFR exome
AF:
0.0190
Gnomad AMR exome
AF:
0.166
Gnomad ASJ exome
AF:
0.102
Gnomad EAS exome
AF:
0.141
Gnomad FIN exome
AF:
0.150
Gnomad NFE exome
AF:
0.0995
Gnomad OTH exome
AF:
0.105
GnomAD4 exome
AF:
0.106
AC:
152415
AN:
1441008
Hom.:
8492
Cov.:
30
AF XY:
0.106
AC XY:
75683
AN XY:
714534
show subpopulations
African (AFR)
AF:
0.0176
AC:
586
AN:
33248
American (AMR)
AF:
0.160
AC:
6576
AN:
41208
Ashkenazi Jewish (ASJ)
AF:
0.0984
AC:
2527
AN:
25684
East Asian (EAS)
AF:
0.128
AC:
5031
AN:
39242
South Asian (SAS)
AF:
0.124
AC:
10216
AN:
82440
European-Finnish (FIN)
AF:
0.151
AC:
7913
AN:
52402
Middle Eastern (MID)
AF:
0.0976
AC:
561
AN:
5750
European-Non Finnish (NFE)
AF:
0.102
AC:
112816
AN:
1101264
Other (OTH)
AF:
0.104
AC:
6189
AN:
59770
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
7154
14308
21461
28615
35769
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
4240
8480
12720
16960
21200
<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
AF:
0.0856
AC:
13040
AN:
152286
Hom.:
720
Cov.:
33
AF XY:
0.0901
AC XY:
6705
AN XY:
74438
show subpopulations
African (AFR)
AF:
0.0208
AC:
865
AN:
41570
American (AMR)
AF:
0.128
AC:
1954
AN:
15296
Ashkenazi Jewish (ASJ)
AF:
0.0988
AC:
343
AN:
3472
East Asian (EAS)
AF:
0.137
AC:
710
AN:
5178
South Asian (SAS)
AF:
0.120
AC:
578
AN:
4826
European-Finnish (FIN)
AF:
0.148
AC:
1567
AN:
10612
Middle Eastern (MID)
AF:
0.0714
AC:
21
AN:
294
European-Non Finnish (NFE)
AF:
0.100
AC:
6834
AN:
68014
Other (OTH)
AF:
0.0762
AC:
161
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
601
1203
1804
2406
3007
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
144
288
432
576
720
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0936
Hom.:
239
Bravo
AF:
0.0826

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.13
DANN
Benign
0.52
PhyloP100
-0.13
Mutation Taster
=15/85
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000059
dbscSNV1_RF
Benign
0.030
SpliceAI score (max)
0.080
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; COSMIC: COSV107310902; API