rs2637777

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005245.4(FAT1):c.10660T>G(p.Ser3554Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 1,613,202 control chromosomes in the GnomAD database, including 132,754 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

Frequency

Genomes: 𝑓 0.49 ( 20534 hom., cov: 32)

Exomes 𝑓: 0.38 ( 112220 hom. )

Consequence

FAT1
NM_005245.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.198

Publications

51 publications found

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]

FAT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.4539924E-6).

BP6

Variant 4-186603866-A-C is Benign according to our data. Variant chr4-186603866-A-C is described in ClinVar as Benign. ClinVar VariationId is 1268969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAT1	NM_005245.4 link	c.10660T>G	p.Ser3554Ala	missense_variant	Exon 19 of 27	ENST00000441802.7	NP_005236.2	Q14517
FAT1	NM_001440456.1 link	c.10660T>G	p.Ser3554Ala	missense_variant	Exon 19 of 28		NP_001427385.1
FAT1	NM_001440457.1 link	c.10660T>G	p.Ser3554Ala	missense_variant	Exon 19 of 28		NP_001427386.1
FAT1	NM_001440455.1 link	c.10660T>G	p.Ser3554Ala	missense_variant	Exon 19 of 27		NP_001427384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAT1	ENST00000441802.7 link	c.10660T>G	p.Ser3554Ala	missense_variant	Exon 19 of 27	5	NM_005245.4	ENSP00000406229.2		Q14517

Frequencies

GnomAD3 genomes

AF:

0.493

AC:

74805

AN:

151844

Hom.:

20495

Cov.:

show subpopulations

Gnomad AFR

AF:

0.733

Gnomad AMI

AF:

0.307

Gnomad AMR

AF:

0.531

Gnomad ASJ

AF:

0.456

Gnomad EAS

AF:

0.614

Gnomad SAS

AF:

0.263

Gnomad FIN

AF:

0.389

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.366

Gnomad OTH

AF:

0.472

GnomAD2 exomes

AF:

0.431

AC:

107450

AN:

249068

AF XY:

0.412

show subpopulations

Gnomad AFR exome

AF:

0.741

Gnomad AMR exome

AF:

0.592

Gnomad ASJ exome

AF:

0.457

Gnomad EAS exome

AF:

0.625

Gnomad FIN exome

AF:

0.385

Gnomad NFE exome

AF:

0.364

Gnomad OTH exome

AF:

0.407

GnomAD4 exome

AF:

0.381

AC:

556329

AN:

1461240

Hom.:

112220

Cov.:

AF XY:

0.375

AC XY:

272645

AN XY:

726910

show subpopulations

African (AFR)

AF:

0.745

AC:

24957

AN:

33478

American (AMR)

AF:

0.582

AC:

26015

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.458

AC:

11958

AN:

26132

East Asian (EAS)

AF:

0.649

AC:

25780

AN:

39698

South Asian (SAS)

AF:

0.259

AC:

22377

AN:

86250

European-Finnish (FIN)

AF:

0.382

AC:

20384

AN:

53398

Middle Eastern (MID)

AF:

0.408

AC:

2351

AN:

5766

European-Non Finnish (NFE)

AF:

0.358

AC:

398306

AN:

1111444

Other (OTH)

AF:

0.401

AC:

24201

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

18568

37136

55703

74271

92839

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12918

25836

38754

51672

64590

<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:

0.493

AC:

74898

AN:

151962

Hom.:

20534

Cov.:

AF XY:

0.493

AC XY:

36597

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.733

AC:

30365

AN:

41404

American (AMR)

AF:

0.532

AC:

8119

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.456

AC:

1581

AN:

3468

East Asian (EAS)

AF:

0.614

AC:

3164

AN:

5152

South Asian (SAS)

AF:

0.263

AC:

1265

AN:

4818

European-Finnish (FIN)

AF:

0.389

AC:

4113

AN:

10582

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.366

AC:

24890

AN:

67956

Other (OTH)

AF:

0.469

AC:

988

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1737

3473

5210

6946

8683

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

630

1260

1890

2520

3150

<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:

0.413

Hom.:

59189

Bravo

AF:

0.522

TwinsUK

AF:

0.341

AC:

1266

ALSPAC

AF:

0.350

AC:

1350

ESP6500AA

AF:

0.708

AC:

2723

ESP6500EA

AF:

0.362

AC:

2990

ExAC

AF:

0.427

AC:

51629

EpiCase

AF:

0.364

EpiControl

AF:

0.365

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.69

(source)

DANN

Benign

0.45

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.24

T;T

MetaRNN

Benign

0.0000015

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.42

N;.

PhyloP100

0.20

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.74

N;.

REVEL

Benign

0.039

Sift

Benign

0.43

T;.

Sift4G

Benign

0.34

T;T

Polyphen

0.0

B;.

Vest4

0.041

MPC

0.079

ClinPred

0.0035

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.055

gMVP

0.15

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over