rs17309806

Positions:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001079802.2(FKTN):c.1026C>A(p.Leu342=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,606,314 control chromosomes in the GnomAD database, including 70,565 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5818 hom., cov: 32)

Exomes 𝑓: 0.29 ( 64747 hom. )

Consequence

FKTN
NM_001079802.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: 0.635

Variant links:

Genes affected

FKTN (HGNC:3622): (fukutin) The protein encoded by this gene is a putative transmembrane protein that is localized to the cis-Golgi compartment, where it may be involved in the glycosylation of alpha-dystroglycan in skeletal muscle. The encoded protein is thought to be a glycosyltransferase and could play a role in brain development. Defects in this gene are a cause of Fukuyama-type congenital muscular dystrophy (FCMD), Walker-Warburg syndrome (WWS), limb-girdle muscular dystrophy type 2M (LGMD2M), and dilated cardiomyopathy type 1X (CMD1X). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2010]

FKTN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 9-105618074-C-A is Benign according to our data. Variant chr9-105618074-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 93510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-105618074-C-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.635 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKTN	NM_001079802.2 linkuse as main transcript	c.1026C>A	p.Leu342=	synonymous_variant	9/11	ENST00000357998.10	NP_001073270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKTN	ENST00000357998.10 linkuse as main transcript	c.1026C>A	p.Leu342=	synonymous_variant	9/11	5	NM_001079802.2	ENSP00000350687	P1	O75072-1

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

41066

AN:

151948

Hom.:

5809

Cov.:

show subpopulations

Gnomad AFR

AF:

0.236

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.290

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.0947

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.275

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.276

GnomAD3 exomes

AF:

0.253

AC:

63477

AN:

250748

Hom.:

8922

AF XY:

0.247

AC XY:

33453

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.234

Gnomad AMR exome

AF:

0.280

Gnomad ASJ exome

AF:

0.285

Gnomad EAS exome

AF:

0.0915

Gnomad SAS exome

AF:

0.0967

Gnomad FIN exome

AF:

0.279

Gnomad NFE exome

AF:

0.308

Gnomad OTH exome

AF:

0.269

GnomAD4 exome

AF:

0.290

AC:

421143

AN:

1454250

Hom.:

64747

Cov.:

AF XY:

0.284

AC XY:

205289

AN XY:

723890

show subpopulations

Gnomad4 AFR exome

AF:

0.235

Gnomad4 AMR exome

AF:

0.279

Gnomad4 ASJ exome

AF:

0.283

Gnomad4 EAS exome

AF:

0.102

Gnomad4 SAS exome

AF:

0.0982

Gnomad4 FIN exome

AF:

0.286

Gnomad4 NFE exome

AF:

0.315

Gnomad4 OTH exome

AF:

0.276

GnomAD4 genome

AF:

0.270

AC:

41114

AN:

152064

Hom.:

5818

Cov.:

AF XY:

0.265

AC XY:

19708

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.236

Gnomad4 AMR

AF:

0.291

Gnomad4 ASJ

AF:

0.276

Gnomad4 EAS

AF:

0.0954

Gnomad4 SAS

AF:

0.105

Gnomad4 FIN

AF:

0.275

Gnomad4 NFE

AF:

0.311

Gnomad4 OTH

AF:

0.277

Alfa

AF:

0.295

Hom.:

13576

Bravo

AF:

0.269

Asia WGS

AF:

0.126

AC:

438

AN:

3478

EpiCase

AF:

0.304

EpiControl

AF:

0.299

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:9

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 16, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 26, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jan 13, 2015	p.Leu342Leu in exon 9 of FKTN: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 31.8% (2731/8596) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs17309806). -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Dilated cardiomyopathy 1X

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 11, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Walker-Warburg congenital muscular dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

7.0

DANN

Benign

0.65

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