NM_001291303.3:c.12855T>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001291303.3(FAT4):c.12855T>C(p.Asp4285Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00487 in 1,613,850 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 31 hom. )

Consequence

FAT4
NM_001291303.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.22

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]

FAT4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 4-125487377-T-C is Benign according to our data. Variant chr4-125487377-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 380888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-125487377-T-C is described in Lovd as [Likely_benign]. Variant chr4-125487377-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.22 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00363 (553/152338) while in subpopulation NFE AF= 0.00554 (377/68034). AF 95% confidence interval is 0.00508. There are 0 homozygotes in gnomad4. There are 250 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAT4	NM_001291303.3 link	c.12855T>C	p.Asp4285Asp	synonymous_variant	Exon 17 of 18	ENST00000394329.9	NP_001278232.1	Q6V0I7A0A6Q8JR05X2G5I7B3KU84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FAT4	ENST00000394329.9 link	c.12855T>C	p.Asp4285Asp	synonymous_variant	Exon 17 of 18	5	NM_001291303.3	ENSP00000377862.4	A0A6Q8JR05
FAT4	ENST00000335110.5 link	c.7572T>C	p.Asp2524Asp	synonymous_variant	Exon 14 of 15	1		ENSP00000335169.5	Q6V0I7-2
FAT4	ENST00000674496.2 link	c.7626T>C	p.Asp2542Asp	synonymous_variant	Exon 16 of 17			ENSP00000501473.2	A0A7P0T1I0

Frequencies

GnomAD3 genomes

AF:

0.00363

AC:

552

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00554

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00495

AC:

1241

AN:

250696

Hom.:

AF XY:

0.00537

AC XY:

728

AN XY:

135626

show subpopulations

Gnomad AFR exome

AF:

0.000812

Gnomad AMR exome

AF:

0.00318

Gnomad ASJ exome

AF:

0.0185

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00435

Gnomad FIN exome

AF:

0.00157

Gnomad NFE exome

AF:

0.00637

Gnomad OTH exome

AF:

0.00689

GnomAD4 exome

AF:

0.00500

AC:

7308

AN:

1461512

Hom.:

Cov.:

AF XY:

0.00513

AC XY:

3727

AN XY:

727020

show subpopulations

Gnomad4 AFR exome

AF:

0.000866

Gnomad4 AMR exome

AF:

0.00322

Gnomad4 ASJ exome

AF:

0.0171

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00398

Gnomad4 FIN exome

AF:

0.00174

Gnomad4 NFE exome

AF:

0.00524

Gnomad4 OTH exome

AF:

0.00528

GnomAD4 genome

AF:

0.00363

AC:

553

AN:

152338

Hom.:

Cov.:

AF XY:

0.00336

AC XY:

250

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.00554

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00656

Hom.:

Bravo

AF:

0.00408

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Sep 07, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FAT4: BP4, BP7, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:2

Jul 05, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Jun 05, 2018

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

FAT4-related disorder

Benign:1

May 15, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

3.7

DANN

Benign

0.58

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over