rs1037406947

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001079802.2(FKTN):c.7A>G(p.Arg3Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,230 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FKTN
NM_001079802.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: 4.36

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive limb-girdle muscular dystrophy type 2M
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, G2P
myopathy caused by variation in FKTN
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
congenital muscular dystrophy without intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
muscle-eye-brain disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
muscular dystrophy-dystroglycanopathy, type A
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
dilated cardiomyopathy 1X
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

FKTN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079802.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FKTN	NM_001079802.2	MANE Select	c.7A>G	p.Arg3Gly	missense	Exon 3 of 11	NP_001073270.1
FKTN	NM_001351496.2		c.7A>G	p.Arg3Gly	missense	Exon 4 of 12	NP_001338425.1
FKTN	NM_006731.2		c.7A>G	p.Arg3Gly	missense	Exon 2 of 10	NP_006722.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FKTN	ENST00000357998.10	TSL:5 MANE Select	c.7A>G	p.Arg3Gly	missense	Exon 3 of 11	ENSP00000350687.6
FKTN	ENST00000223528.6	TSL:1	c.7A>G	p.Arg3Gly	missense	Exon 2 of 10	ENSP00000223528.2
FKTN	ENST00000602526.1	TSL:1	n.7A>G		non_coding_transcript_exon	Exon 1 of 11	ENSP00000473347.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.00e-7

AC:

AN:

1427988

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

712738

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32730

American (AMR)

AF:

0.00

AC:

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25884

East Asian (EAS)

AF:

0.00

AC:

AN:

39476

South Asian (SAS)

AF:

0.00

AC:

AN:

85556

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1081288

Other (OTH)

AF:

0.0000169

AC:

AN:

59284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41462

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5206

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Walker-Warburg congenital muscular dystrophy (2)

Cardiovascular phenotype (1)

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4;C1969024:Dilated cardiomyopathy 1X;C1969040:Autosomal recessive limb-girdle muscular dystrophy type 2M;C2751052:Muscular dystrophy-dystroglycanopathy (congenital without intellectual disability), type B4;C4284790:Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.73

M_CAP

Uncertain

0.18

MetaRNN

Uncertain

0.43

MetaSVM

Uncertain

0.49

MutationAssessor

Benign

1.9

PhyloP100

4.4

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.49

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0080

Polyphen

0.32

Vest4

0.49

MutPred

0.37

Loss of MoRF binding (P = 8e-04)

MVP

0.89

MPC

0.13

ClinPred

0.80

GERP RS

5.2

PromoterAI

0.021

Neutral

(source)

Varity_R

0.12

gMVP

0.73

Mutation Taster

=57/43

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over