NM_001079802.2:c.106-3657T>C

Variant names:

• chr9-105592941-T-C
• rs1960023
• NM_001079802.2:c.106-3657T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001079802.2(FKTN):​c.106-3657T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 152,056 control chromosomes in the GnomAD database, including 26,513 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (26513 hom., cov: 32)
• Consequence: FKTN NM_001079802.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.725
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKTN	NM_001079802.2	c.106-3657T>C		intron_variant	Intron 3 of 10	ENST00000357998.10	NP_001073270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKTN	ENST00000357998.10	c.106-3657T>C		intron_variant	Intron 3 of 10	5	NM_001079802.2	ENSP00000350687.6

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89352 AN: 151938 Hom.: 26482 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.603

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.588 AC: 89435 AN: 152056 Hom.: 26513 Cov.: 32 AF XY: 0.587 AC XY: 43602 AN XY: 74316

African (AFR) AF: 0.593 AC: 24602 AN: 41470

American (AMR) AF: 0.643 AC: 9828 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1897 AN: 3470

East Asian (EAS) AF: 0.704 AC: 3642 AN: 5172

South Asian (SAS) AF: 0.438 AC: 2115 AN: 4826

European-Finnish (FIN) AF: 0.590 AC: 6229 AN: 10554

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39263 AN: 67970

Other (OTH) AF: 0.605 AC: 1276 AN: 2110

Alfa AF: 0.583 Hom.: 3176

Bravo AF: 0.598

Asia WGS AF: 0.570 AC: 1987 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.48
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1960023; hg19: chr9-108355222;