chr9-105573627-CA-C

Position:

• chr9-105573627-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001079802.2(FKTN):​c.-180-15delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 134,948 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Likely benign (★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.011 (11 hom., cov: 31)
  • Exomes 𝑓: 0.31 (0 hom.)
• Consequence: FKTN NM_001079802.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.268

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 9-105573627-CA-C is Benign according to our data. Variant chr9-105573627-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 1212618.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKTN	NM_001079802.2	c.-180-15delA		intron_variant		ENST00000357998.10	NP_001073270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKTN	ENST00000357998.10	c.-180-15delA		intron_variant		5	NM_001079802.2	ENSP00000350687.6

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 1504 AN: 134892 Hom.: 11 Cov.: 31

Gnomad AFR AF: 0.00296

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0146

Gnomad ASJ AF: 0.0240

Gnomad EAS AF: 0.00104

Gnomad SAS AF: 0.0245

Gnomad FIN AF: 0.0208

Gnomad MID AF: 0.0298

Gnomad NFE AF: 0.0132

Gnomad OTH AF: 0.0160

GnomAD4 exome AF: 0.313 AC: 5 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 3 AN XY: 12

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0112 AC: 1505 AN: 134932 Hom.: 11 Cov.: 31 AF XY: 0.0120 AC XY: 779 AN XY: 65084

Gnomad4 AFR AF: 0.00296

Gnomad4 AMR AF: 0.0146

Gnomad4 ASJ AF: 0.0240

Gnomad4 EAS AF: 0.00104

Gnomad4 SAS AF: 0.0250

Gnomad4 FIN AF: 0.0208

Gnomad4 NFE AF: 0.0132

Gnomad4 OTH AF: 0.0159

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 30, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BranchPoint Hunter		4.0

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

LitVar

Other links and lift over

dbSNP: rs796889209; hg19: chr9-108335908;