dbSNP rs118064041: FKTN:c.1044+44A>G (chr9-105618136-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001079802.2(FKTN):c.1044+44A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0323 in 1,509,854 control chromosomes in the GnomAD database, including 904 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 58 hom., cov: 32)

Exomes 𝑓: 0.033 ( 846 hom. )

Consequence

FKTN
NM_001079802.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.363

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: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 9-105618136-A-G is Benign according to our data. Variant chr9-105618136-A-G is described in ClinVar as Benign. ClinVar VariationId is 260021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0243 (3699/152192) while in subpopulation NFE AF = 0.0385 (2619/67998). AF 95% confidence interval is 0.0373. There are 58 homozygotes in GnomAd4. There are 1689 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 58 AR,AD gene

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	Effect	Exon Rank	Protein	UniProt
FKTN	NM_001079802.2	MANE Select	c.1044+44A>G	intron	N/A	NP_001073270.1	O75072-1
FKTN	NM_001351496.2		c.1044+44A>G	intron	N/A	NP_001338425.1	O75072-1
FKTN	NM_006731.2		c.1044+44A>G	intron	N/A	NP_006722.2	O75072-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FKTN	ENST00000357998.10	TSL:5 MANE Select	c.1044+44A>G	intron	N/A	ENSP00000350687.6	O75072-1
FKTN	ENST00000223528.6	TSL:1	c.1044+44A>G	intron	N/A	ENSP00000223528.2	O75072-1
FKTN	ENST00000602526.1	TSL:1	n.*1082+44A>G	intron	N/A	ENSP00000473347.1	R4GMU0

Frequencies

GnomAD3 genomes

AF:

0.0243

AC:

3698

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00688

Gnomad AMI

AF:

0.0198

Gnomad AMR

AF:

0.0173

Gnomad ASJ

AF:

0.0337

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00747

Gnomad FIN

AF:

0.0281

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0385

Gnomad OTH

AF:

0.0279

GnomAD2 exomes

AF:

0.0267

AC:

6635

AN:

248588

AF XY:

0.0271

show subpopulations

Gnomad AFR exome

AF:

0.00672

Gnomad AMR exome

AF:

0.0152

Gnomad ASJ exome

AF:

0.0297

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0314

Gnomad NFE exome

AF:

0.0409

Gnomad OTH exome

AF:

0.0258

GnomAD4 exome

AF:

0.0332

AC:

45085

AN:

1357662

Hom.:

846

Cov.:

AF XY:

0.0327

AC XY:

22292

AN XY:

681274

show subpopulations

African (AFR)

AF:

0.00536

AC:

169

AN:

31550

American (AMR)

AF:

0.0161

AC:

714

AN:

44484

Ashkenazi Jewish (ASJ)

AF:

0.0283

AC:

717

AN:

25312

East Asian (EAS)

AF:

0.0000515

AC:

AN:

38862

South Asian (SAS)

AF:

0.00952

AC:

803

AN:

84378

European-Finnish (FIN)

AF:

0.0316

AC:

1669

AN:

52836

Middle Eastern (MID)

AF:

0.00911

AC:

AN:

5596

European-Non Finnish (NFE)

AF:

0.0387

AC:

39387

AN:

1017950

Other (OTH)

AF:

0.0277

AC:

1573

AN:

56694

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

1747

3495

5242

6990

8737

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1338

2676

4014

5352

6690

<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:

0.0243

AC:

3699

AN:

152192

Hom.:

Cov.:

AF XY:

0.0227

AC XY:

1689

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.00686

AC:

285

AN:

41550

American (AMR)

AF:

0.0173

AC:

264

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0337

AC:

117

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.00768

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0281

AC:

298

AN:

10594

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0385

AC:

2619

AN:

67998

Other (OTH)

AF:

0.0276

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

175

351

526

702

877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0334

Hom.:

Bravo

AF:

0.0241

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

8.4

(source)

DANN

Benign

0.73

PhyloP100

0.36

PromoterAI

-0.0041

Neutral

(source)

Mutation Taster

=100/0

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

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over