rs145883833

Positions:

• chr9-105619894-C-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001079802.2(FKTN):​c.1045-40C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00391 in 1,572,446 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (27 hom.)
• Consequence: FKTN NM_001079802.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.242

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 9-105619894-C-A is Benign according to our data. Variant chr9-105619894-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 93511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-105619894-C-A is described in Lovd as [Benign].
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKTN	NM_001079802.2	c.1045-40C>A		intron_variant		ENST00000357998.10	NP_001073270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKTN	ENST00000357998.10	c.1045-40C>A		intron_variant		5	NM_001079802.2	ENSP00000350687	P1

Frequencies

GnomAD3 genomes AF: 0.00303 AC: 460 AN: 151890 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000580

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00302

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00833

Gnomad FIN AF: 0.000757

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00380

Gnomad OTH AF: 0.00240

GnomAD3 exomes AF: 0.00387 AC: 944 AN: 243786 Hom.: 8 AF XY: 0.00411 AC XY: 542 AN XY: 131716

Gnomad AFR exome AF: 0.000631

Gnomad AMR exome AF: 0.00197

Gnomad ASJ exome AF: 0.0218

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00788

Gnomad FIN exome AF: 0.000802

Gnomad NFE exome AF: 0.00343

Gnomad OTH exome AF: 0.00519

GnomAD4 exome AF: 0.00401 AC: 5692 AN: 1420440 Hom.: 27 Cov.: 24 AF XY: 0.00415 AC XY: 2941 AN XY: 707958

Gnomad4 AFR exome AF: 0.000462

Gnomad4 AMR exome AF: 0.00218

Gnomad4 ASJ exome AF: 0.0233

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00808

Gnomad4 FIN exome AF: 0.00134

Gnomad4 NFE exome AF: 0.00361

Gnomad4 OTH exome AF: 0.00532

GnomAD4 genome AF: 0.00303 AC: 461 AN: 152006 Hom.: 2 Cov.: 32 AF XY: 0.00289 AC XY: 215 AN XY: 74306

Gnomad4 AFR AF: 0.000579

Gnomad4 AMR AF: 0.00301

Gnomad4 ASJ AF: 0.0225

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00855

Gnomad4 FIN AF: 0.000757

Gnomad4 NFE AF: 0.00380

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00506 Hom.: 1

Bravo AF: 0.00314

Asia WGS AF: 0.00434 AC: 15 AN: 3472

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 31, 2012	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	9.5
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs145883833; hg19: chr9-108382175;