4-186588777-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005245.4(FAT1):​c.13582G>C​(p.Glu4528Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E4528K) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

FAT1
NM_005245.4 missense

Scores

1
2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.38
Variant links:
Genes affected
FAT1 (HGNC:3595): (FAT atypical cadherin 1) This gene is an ortholog of the Drosophila fat gene, which encodes a tumor suppressor essential for controlling cell proliferation during Drosophila development. The gene product is a member of the cadherin superfamily, a group of integral membrane proteins characterized by the presence of cadherin-type repeats. In addition to containing 34 tandem cadherin-type repeats, the gene product has five epidermal growth factor (EGF)-like repeats and one laminin A-G domain. This gene is expressed at high levels in a number of fetal epithelia. Its product probably functions as an adhesion molecule and/or signaling receptor, and is likely to be important in developmental processes and cell communication. Transcript variants derived from alternative splicing and/or alternative promoter usage exist, but they have not been fully described. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.20849511).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAT1NM_005245.4 linkc.13582G>C p.Glu4528Gln missense_variant Exon 27 of 27 ENST00000441802.7 NP_005236.2 Q14517
FAT1XM_005262834.4 linkc.13618G>C p.Glu4540Gln missense_variant Exon 28 of 28 XP_005262891.1
FAT1XM_005262835.3 linkc.13618G>C p.Glu4540Gln missense_variant Exon 28 of 28 XP_005262892.1
FAT1XM_006714139.4 linkc.13582G>C p.Glu4528Gln missense_variant Exon 27 of 27 XP_006714202.1 Q14517

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAT1ENST00000441802.7 linkc.13582G>C p.Glu4528Gln missense_variant Exon 27 of 27 5 NM_005245.4 ENSP00000406229.2 Q14517
FAT1ENST00000512772.5 linkc.919G>C p.Glu307Gln missense_variant Exon 4 of 4 2 ENSP00000424157.1 H0Y9H4
FAT1ENST00000500085.2 linkn.1274G>C non_coding_transcript_exon_variant Exon 3 of 3 2
FAT1ENST00000507105.1 linkc.*30G>C downstream_gene_variant 3 ENSP00000423801.1 H0Y9C8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
19
DANN
Benign
0.96
DEOGEN2
Benign
0.12
T;T
Eigen
Benign
0.17
Eigen_PC
Benign
0.14
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.83
T;T
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.21
T;T
MetaSVM
Benign
-0.48
T
MutationAssessor
Uncertain
2.3
M;.
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.87
N;.
REVEL
Benign
0.18
Sift
Benign
0.15
T;.
Sift4G
Uncertain
0.040
D;D
Polyphen
0.61
P;.
Vest4
0.21
MutPred
0.098
Gain of glycosylation at Y4523 (P = 0.0191);.;
MVP
0.39
MPC
0.16
ClinPred
0.46
T
GERP RS
5.4
Varity_R
0.14
gMVP
0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-187509931; API