rs145883833

Variant names:

• chr9-105619894-C-A
• rs145883833
• NM_001079802.2:c.1045-40C>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001079802.2(FKTN):​c.1045-40C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00391 in 1,572,446 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (27 hom.)
• Consequence: FKTN NM_001079802.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.242
• 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 9-105619894-C-A is Benign according to our data. Variant chr9-105619894-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 93511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKTN	NM_001079802.2	c.1045-40C>A		intron_variant	Intron 9 of 10	ENST00000357998.10	NP_001073270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKTN	ENST00000357998.10	c.1045-40C>A		intron_variant	Intron 9 of 10	5	NM_001079802.2	ENSP00000350687.6

Frequencies

GnomAD3 genomes AF: 0.00303 AC: 460 AN: 151890 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000580

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00302

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00833

Gnomad FIN AF: 0.000757

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00380

Gnomad OTH AF: 0.00240

GnomAD2 exomes AF: 0.00387 AC: 944 AN: 243786 AF XY: 0.00411

Gnomad AFR exome AF: 0.000631

Gnomad AMR exome AF: 0.00197

Gnomad ASJ exome AF: 0.0218

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000802

Gnomad NFE exome AF: 0.00343

Gnomad OTH exome AF: 0.00519

GnomAD4 exome AF: 0.00401 AC: 5692 AN: 1420440 Hom.: 27 Cov.: 24 AF XY: 0.00415 AC XY: 2941 AN XY: 707958

African (AFR) AF: 0.000462 AC: 15 AN: 32498

American (AMR) AF: 0.00218 AC: 95 AN: 43572

Ashkenazi Jewish (ASJ) AF: 0.0233 AC: 595 AN: 25548

East Asian (EAS) AF: 0.00 AC: 0 AN: 39120

South Asian (SAS) AF: 0.00808 AC: 663 AN: 82058

European-Finnish (FIN) AF: 0.00134 AC: 70 AN: 52408

Middle Eastern (MID) AF: 0.00653 AC: 37 AN: 5666

European-Non Finnish (NFE) AF: 0.00361 AC: 3904 AN: 1080766

Other (OTH) AF: 0.00532 AC: 313 AN: 58804

GnomAD4 genome AF: 0.00303 AC: 461 AN: 152006 Hom.: 2 Cov.: 32 AF XY: 0.00289 AC XY: 215 AN XY: 74306

African (AFR) AF: 0.000579 AC: 24 AN: 41468

American (AMR) AF: 0.00301 AC: 46 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00855 AC: 41 AN: 4798

European-Finnish (FIN) AF: 0.000757 AC: 8 AN: 10562

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00380 AC: 258 AN: 67958

Other (OTH) AF: 0.00237 AC: 5 AN: 2108

Alfa AF: 0.00506 Hom.: 1

Bravo AF: 0.00314

Asia WGS AF: 0.00434 AC: 15 AN: 3472

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Aug 31, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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PreventionGenetics, part of Exact Sciences

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	-0.68
CADD	Benign	9.5
DANN	Benign	0.71
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs145883833; hg19: chr9-108382175;