9-105618136-A-C

Variant names:

• chr9-105618136-A-C
• rs118064041
• NM_001079802.2:c.1044+44A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001079802.2(FKTN):​c.1044+44A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00054 in 1,358,666 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.00054 (0 hom.)
• Consequence: FKTN NM_001079802.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.363
• Publications: 0 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: 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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKTN	NM_001079802.2	MANE Select	c.1044+44A>C		intron	N/A	NP_001073270.1	O75072-1
	FKTN	NM_001351496.2		c.1044+44A>C		intron	N/A	NP_001338425.1	O75072-1
	FKTN	NM_006731.2		c.1044+44A>C		intron	N/A	NP_006722.2	O75072-1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.000540 AC: 734 AN: 1358666 Hom.: 0 Cov.: 22 AF XY: 0.000554 AC XY: 378 AN XY: 681774

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000476 AC: 15 AN: 31540

American (AMR) AF: 0.0000450 AC: 2 AN: 44482

Ashkenazi Jewish (ASJ) AF: 0.000316 AC: 8 AN: 25314

East Asian (EAS) AF: 0.000129 AC: 5 AN: 38852

South Asian (SAS) AF: 0.000225 AC: 19 AN: 84376

European-Finnish (FIN) AF: 0.0000946 AC: 5 AN: 52836

Middle Eastern (MID) AF: 0.000536 AC: 3 AN: 5594

European-Non Finnish (NFE) AF: 0.000640 AC: 652 AN: 1018972

Other (OTH) AF: 0.000441 AC: 25 AN: 56700

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.9
DANN	Benign	0.73
PhyloP100		0.36
PromoterAI		0.00090	Neutral

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: rs118064041; hg19: chr9-108380417;