rs885954

Positions:

• chr9-105647119-A-C
• chr9-105647119-A-T

Variant summary

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

The ENST00000676310.1(FKTN):​c.1271-4953A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,998 control chromosomes in the GnomAD database, including 12,702 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 0.40 (12702 hom., cov: 32)
• Consequence: FKTN ENST00000676310.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.105647119A>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKTN	ENST00000676310.1	c.1271-4953A>C		intron_variant				ENSP00000501585.1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60220 AN: 151880 Hom.: 12678 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.397 AC: 60276 AN: 151998 Hom.: 12702 Cov.: 32 AF XY: 0.394 AC XY: 29269 AN XY: 74294

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.429

Alfa AF: 0.443 Hom.: 22255

Bravo AF: 0.402

Asia WGS AF: 0.274 AC: 952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs885954; hg19: chr9-108409400;