rs2518108

chr9-105643816-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000676310.1(FKTN):c.1271-8256A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 152,106 control chromosomes in the GnomAD database, including 12,630 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 0.39 (12630 hom., cov: 33)
• Consequence: FKTN ENST00000676310.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.649

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FKTN	ENST00000674633.1	c.1271-888A>T		intron_variant
FKTN	ENST00000676310.1	c.1271-8256A>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.395 AC: 60020 AN: 151988 Hom.: 12607 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.395 AC: 60075 AN: 152106 Hom.: 12630 Cov.: 33 AF XY: 0.392 AC XY: 29168 AN XY: 74340

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.433

Alfa AF: 0.437 Hom.: 1822

Bravo AF: 0.399

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.68
Dann	Benign	0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2518108; hg19: chr9-108406097;