chr9-105575062-G-A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBP6

The NM_001079802.2(FKTN):​c.30G>A​(p.Leu10Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000186 in 1,610,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

FKTN
NM_001079802.2 synonymous

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 6.64

Publications

1 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
Variant 9-105575062-G-A is Benign according to our data. Variant chr9-105575062-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 528835.We mark this variant Likely_benign, oryginal submission is: [Conflicting_classifications_of_pathogenicity].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FKTNNM_001079802.2 linkc.30G>A p.Leu10Leu synonymous_variant Exon 3 of 11 ENST00000357998.10 NP_001073270.1 O75072-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FKTNENST00000357998.10 linkc.30G>A p.Leu10Leu synonymous_variant Exon 3 of 11 5 NM_001079802.2 ENSP00000350687.6 O75072-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152154
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000962
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
GnomAD2 exomes
AF:
0.0000278
AC:
7
AN:
251352
AF XY:
0.0000442
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000381
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000171
AC:
25
AN:
1457758
Hom.:
0
Cov.:
28
AF XY:
0.0000138
AC XY:
10
AN XY:
725510
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33366
American (AMR)
AF:
0.00
AC:
0
AN:
44704
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26094
East Asian (EAS)
AF:
0.000606
AC:
24
AN:
39612
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86168
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53414
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5756
European-Non Finnish (NFE)
AF:
9.02e-7
AC:
1
AN:
1108408
Other (OTH)
AF:
0.00
AC:
0
AN:
60236
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.449
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000328
AC:
5
AN:
152272
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74452
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41574
American (AMR)
AF:
0.00
AC:
0
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.000964
AC:
5
AN:
5188
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4816
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10600
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68012
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00
Hom.:
0
Bravo
AF:
0.0000491

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Uncertain:1
Mar 23, 2018
Eurofins Ntd Llc (ga)
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Cardiovascular phenotype Benign:1
Dec 14, 2024
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This alteration is classified as likely 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
Feb 23, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.36
CADD
Benign
14
DANN
Benign
0.80
PhyloP100
6.6
PromoterAI
-0.042
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs202047149; hg19: chr9-108337343; API