9-105573677-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001079802.2(FKTN):c.-158G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 151,944 control chromosomes in the GnomAD database, including 5,531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5531 hom., cov: 32)
  • Exomes 𝑓: 0.30 (0 hom.)
• Consequence: FKTN NM_001079802.2 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.836

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 9-105573677-G-C is Benign according to our data. Variant chr9-105573677-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 364484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FKTN	NM_001079802.2	c.-158G>C		5_prime_UTR_variant	2/11	ENST00000357998.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FKTN	ENST00000357998.10	c.-158G>C		5_prime_UTR_variant	2/11	5	NM_001079802.2	P1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39911 AN: 151816 Hom.: 5526 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.0628

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.273

GnomAD4 exome AF: 0.300 AC: 3 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.375 AC XY: 3 AN XY: 8

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.263 AC: 39945 AN: 151934 Hom.: 5531 Cov.: 32 AF XY: 0.256 AC XY: 19028 AN XY: 74266

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.0634

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.274

Alfa AF: 0.290 Hom.: 860

Bravo AF: 0.260

Asia WGS AF: 0.112 AC: 389 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Dilated cardiomyopathy 1X Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.7
Dann	Benign	0.65

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: rs4742953; hg19: chr9-108335958;