4-186588714-C-G

Variant names:

• chr4-186588714-C-G
• NM_005245.4:c.13645G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005245.4(FAT1):​c.13645G>C​(p.Val4549Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.68

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31061876).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAT1	NM_005245.4	c.13645G>C	p.Val4549Leu	missense_variant	Exon 27 of 27	ENST00000441802.7	NP_005236.2
FAT1	XM_005262834.4	c.13681G>C	p.Val4561Leu	missense_variant	Exon 28 of 28		XP_005262891.1
FAT1	XM_005262835.3	c.13681G>C	p.Val4561Leu	missense_variant	Exon 28 of 28		XP_005262892.1
FAT1	XM_006714139.4	c.13645G>C	p.Val4549Leu	missense_variant	Exon 27 of 27		XP_006714202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAT1	ENST00000441802.7	c.13645G>C	p.Val4549Leu	missense_variant	Exon 27 of 27	5	NM_005245.4	ENSP00000406229.2
FAT1	ENST00000512772.5	c.982G>C	p.Val328Leu	missense_variant	Exon 4 of 4	2		ENSP00000424157.1
FAT1	ENST00000500085.2	n.1337G>C		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	0.26
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.080	T;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.60	N;.
REVEL	Benign	0.14
Sift	Benign	0.033	D;.
Sift4G	Uncertain	0.051	T;T
Polyphen		0.72	P;.
Vest4		0.31
MutPred		0.12		Gain of glycosylation at S4545 (P = 0.0523);.;
MVP		0.32
MPC		0.12
ClinPred		0.59	D
GERP RS		5.5
Varity_R		0.18
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: chr4-187509868;