chr9-105573789-T-C

Position:

• chr9-105573789-T-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.-89+43T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,176 control chromosomes in the GnomAD database, including 1,487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1487 hom., cov: 32)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: FKTN NM_001079802.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.502

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=-0.89).
• BP6: Variant 9-105573789-T-C is Benign according to our data. Variant chr9-105573789-T-C is described in ClinVar as [Benign]. Clinvar id is 1242033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FKTN	NM_001079802.2	c.-89+43T>C		intron_variant		ENST00000357998.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FKTN	ENST00000357998.10	c.-89+43T>C		intron_variant		5	NM_001079802.2	P1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18778 AN: 152050 Hom.: 1485 Cov.: 32

Gnomad AFR AF: 0.0320

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.150

GnomAD4 exome AF: 0.100 AC: 1 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.100

GnomAD4 genome AF: 0.123 AC: 18782 AN: 152166 Hom.: 1487 Cov.: 32 AF XY: 0.126 AC XY: 9360 AN XY: 74386

Gnomad4 AFR AF: 0.0320

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.150

Alfa AF: 0.123 Hom.: 245

Bravo AF: 0.129

Asia WGS AF: 0.146 AC: 506 AN: 3478

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

Jun 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.0
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2518122; hg19: chr9-108336070;