4-125408758-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001291303.3(FAT4):​c.5884A>G​(p.Thr1962Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

FAT4
NM_001291303.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.96
Variant links:
Genes affected
FAT4 (HGNC:23109): (FAT atypical cadherin 4) The protein encoded by this gene is a member of the protocadherin family. This gene may play a role in regulating planar cell polarity (PCP). Studies in mice suggest that loss of PCP signaling may cause cystic kidney disease, and mutations in this gene have been associated with Van Maldergem Syndrome 2. Alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Mar 2014]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06526536).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FAT4NM_001291303.3 linkuse as main transcriptc.5884A>G p.Thr1962Ala missense_variant 5/18 ENST00000394329.9 NP_001278232.1 Q6V0I7A0A6Q8JR05X2G5I7B3KU84

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FAT4ENST00000394329.9 linkuse as main transcriptc.5884A>G p.Thr1962Ala missense_variant 5/185 NM_001291303.3 ENSP00000377862.4 A0A6Q8JR05
FAT4ENST00000335110.5 linkuse as main transcriptc.778A>G p.Thr260Ala missense_variant 4/151 ENSP00000335169.5 Q6V0I7-2
FAT4ENST00000674496.2 linkuse as main transcriptc.655A>G p.Thr219Ala missense_variant 4/17 ENSP00000501473.2 A0A7P0T1I0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.061
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
16
DANN
Benign
0.89
DEOGEN2
Benign
0.074
T;.
Eigen
Benign
-0.40
Eigen_PC
Benign
-0.23
FATHMM_MKL
Benign
0.73
D
LIST_S2
Benign
0.52
T;T
M_CAP
Benign
0.0036
T
MetaRNN
Benign
0.065
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.1
L;.
MutationTaster
Benign
0.89
N;N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.64
N;N
REVEL
Benign
0.061
Sift
Benign
0.68
T;T
Sift4G
Benign
0.29
T;T
Polyphen
0.0040
B;B
Vest4
0.064
MutPred
0.41
Loss of loop (P = 0.1242);.;
MVP
0.10
MPC
0.15
ClinPred
0.097
T
GERP RS
4.0
Varity_R
0.059
gMVP
0.18

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: rs749792331; hg19: chr4-126329913; API