rs75079578

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_024301.5(FKRP):c.585C>T(p.Asp195Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,579,756 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 19 hom., cov: 33)

Exomes 𝑓: 0.00099 ( 20 hom. )

Consequence

FKRP
NM_024301.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: -3.01

Variant links:

Genes affected

FKRP (HGNC:17997): (fukutin related protein) This gene encodes a protein which is targeted to the medial Golgi apparatus and is necessary for posttranslational modification of dystroglycan. Mutations in this gene have been associated with congenital muscular dystrophy, cognitive disability, and cerebellar cysts. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Oct 2008]

FKRP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 19-46756035-C-T is Benign according to our data. Variant chr19-46756035-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 96112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-46756035-C-T is described in Lovd as [Pathogenic]. Variant chr19-46756035-C-T is described in Lovd as [Benign]. Variant chr19-46756035-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-3.01 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00997 (1516/152028) while in subpopulation AFR AF= 0.0325 (1350/41492). AF 95% confidence interval is 0.0311. There are 19 homozygotes in gnomad4. There are 686 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKRP	NM_024301.5 link	c.585C>T	p.Asp195Asp	synonymous_variant	Exon 4 of 4	ENST00000318584.10	NP_077277.1	Q9H9S5A0A024R0R7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKRP	ENST00000318584.10 link	c.585C>T	p.Asp195Asp	synonymous_variant	Exon 4 of 4	1	NM_024301.5	ENSP00000326570.4		Q9H9S5

Frequencies

GnomAD3 genomes

AF:

0.00995

AC:

1511

AN:

151918

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0325

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00825

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00204

AC:

398

AN:

194854

Hom.:

AF XY:

0.00158

AC XY:

172

AN XY:

108910

show subpopulations

Gnomad AFR exome

AF:

0.0317

Gnomad AMR exome

AF:

0.00161

Gnomad ASJ exome

AF:

0.000906

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000369

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000126

Gnomad OTH exome

AF:

0.00120

GnomAD4 exome

AF:

0.000987

AC:

1409

AN:

1427728

Hom.:

Cov.:

AF XY:

0.000816

AC XY:

579

AN XY:

709610

show subpopulations

Gnomad4 AFR exome

AF:

0.0332

Gnomad4 AMR exome

AF:

0.00206

Gnomad4 ASJ exome

AF:

0.000902

Gnomad4 EAS exome

AF:

0.0000261

Gnomad4 SAS exome

AF:

0.0000360

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000716

Gnomad4 OTH exome

AF:

0.00239

GnomAD4 genome

AF:

0.00997

AC:

1516

AN:

152028

Hom.:

Cov.:

AF XY:

0.00923

AC XY:

686

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0325

Gnomad4 AMR

AF:

0.00818

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00334

Hom.:

Bravo

AF:

0.0115

Asia WGS

AF:

0.00290

AC:

AN:

3458

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Nov 11, 2015

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 24, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Sep 21, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 19, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 12, 2022

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:4

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Autosomal recessive limb-girdle muscular dystrophy type 2I;C1847759:Muscular dystrophy-dystroglycanopathy type B5;C3150413:Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5;C4284790:Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1

Benign:1

Jul 21, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype

Benign:1

Dec 24, 2018

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Walker-Warburg congenital muscular dystrophy

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

5.8

DANN

Benign

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over