chr9-105573627-C-CA

Position:

• chr9-105573627-C-CA

Variant summary

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

The NM_001079802.2(FKTN):​c.-180-15dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0217 in 135,238 control chromosomes in the GnomAD database, including 100 homozygotes. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.022 (100 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FKTN NM_001079802.2 intron
• Clinical Significance: 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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 9-105573627-C-CA is Benign according to our data. Variant chr9-105573627-C-CA is described in ClinVar as [Benign]. Clinvar id is 1249258.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0662 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKTN	ENST00000357998.10	c.-180-28_-180-27insA		intron_variant		5	NM_001079802.2	ENSP00000350687.6

Frequencies

GnomAD3 genomes AF: 0.0215 AC: 2910 AN: 135196 Hom.: 96 Cov.: 31

Gnomad AFR AF: 0.0679

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00820

Gnomad ASJ AF: 0.000623

Gnomad EAS AF: 0.00457

Gnomad SAS AF: 0.00979

Gnomad FIN AF: 0.00168

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00308

Gnomad OTH AF: 0.0176

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 18 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 14

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0217 AC: 2935 AN: 135238 Hom.: 100 Cov.: 31 AF XY: 0.0214 AC XY: 1395 AN XY: 65258

Gnomad4 AFR AF: 0.0684

Gnomad4 AMR AF: 0.00819

Gnomad4 ASJ AF: 0.000623

Gnomad4 EAS AF: 0.00459

Gnomad4 SAS AF: 0.00983

Gnomad4 FIN AF: 0.00168

Gnomad4 NFE AF: 0.00308

Gnomad4 OTH AF: 0.0181

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 24, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BranchPoint Hunter		4.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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;