4-186588652-G-C

Variant summary

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

The NM_005245.4(FAT1):​c.13707C>G​(p.Asp4569Glu) 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. 16/21 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

FAT1
NM_005245.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.08
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 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=0.04908219).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAT1NM_005245.4 linkc.13707C>G p.Asp4569Glu missense_variant Exon 27 of 27 ENST00000441802.7 NP_005236.2 Q14517
FAT1XM_005262834.4 linkc.13743C>G p.Asp4581Glu missense_variant Exon 28 of 28 XP_005262891.1
FAT1XM_005262835.3 linkc.13743C>G p.Asp4581Glu missense_variant Exon 28 of 28 XP_005262892.1
FAT1XM_006714139.4 linkc.13707C>G p.Asp4569Glu 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.13707C>G p.Asp4569Glu missense_variant Exon 27 of 27 5 NM_005245.4 ENSP00000406229.2 Q14517
FAT1ENST00000512772.5 linkc.1044C>G p.Asp348Glu missense_variant Exon 4 of 4 2 ENSP00000424157.1 H0Y9H4
FAT1ENST00000500085.2 linkn.1399C>G non_coding_transcript_exon_variant Exon 3 of 3 2

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
0.094
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
0.0010
DANN
Benign
0.35
DEOGEN2
Benign
0.064
T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.86
D;D
M_CAP
Benign
0.041
D
MetaRNN
Benign
0.049
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.46
N;.
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-0.14
N;.
REVEL
Benign
0.14
Sift
Benign
1.0
T;.
Sift4G
Benign
0.92
T;T
Polyphen
0.062
B;.
Vest4
0.055
MutPred
0.27
Gain of glycosylation at Y4564 (P = 7e-04);.;
MVP
0.18
MPC
0.095
ClinPred
0.056
T
GERP RS
-6.7
Varity_R
0.049
gMVP
0.087

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: chr4-187509806; API