Variant chr19-46755463-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024301.5(FKRP):c.13C>A(p.Arg5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,607,084 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FKRP
NM_024301.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.831

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FKRP	NM_024301.5 linkuse as main transcript	c.13C>A	p.Arg5Ser	missense_variant	4/4	ENST00000318584.10	NP_077277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKRP	ENST00000318584.10 linkuse as main transcript	c.13C>A	p.Arg5Ser	missense_variant	4/4	1	NM_024301.5	ENSP00000326570	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1454862

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723890

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

0.0

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

.;T;.;.;.;.;T;.;.;.;.;.;.;.;.;.;T

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.85

D;.;T;T;T;T;T;T;T;T;D;D;D;T;T;T;T

M_CAP

Pathogenic

0.55

MetaRNN

Uncertain

0.43

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Pathogenic

1.1

MutationAssessor

Benign

1.2

.;L;.;.;.;.;L;.;.;.;.;.;.;.;.;.;.

MutationTaster

Benign

0.79

D;D

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.86

.;N;.;.;.;.;N;.;.;.;.;.;.;.;.;.;.

REVEL

Uncertain

0.48

Sift

Benign

0.040

.;D;.;.;.;.;D;.;.;.;.;.;.;.;.;.;.

Sift4G

Benign

0.30

T;T;D;D;D;D;T;D;D;D;D;D;D;D;D;D;D

Polyphen

0.92

.;P;.;.;.;.;P;.;.;.;.;.;.;.;.;.;.

Vest4

0.41, 0.45

MutPred

0.41

Gain of glycosylation at R5 (P = 0.0024);Gain of glycosylation at R5 (P = 0.0024);Gain of glycosylation at R5 (P = 0.0024);Gain of glycosylation at R5 (P = 0.0024);Gain of glycosylation at R5 (P = 0.0024);Gain of glycosylation at R5 (P = 0.0024);Gain of glycosylation at R5 (P = 0.0024);Gain of glycosylation at R5 (P = 0.0024);Gain of glycosylation at R5 (P = 0.0024);Gain of glycosylation at R5 (P = 0.0024);Gain of glycosylation at R5 (P = 0.0024);Gain of glycosylation at R5 (P = 0.0024);Gain of glycosylation at R5 (P = 0.0024);Gain of glycosylation at R5 (P = 0.0024);Gain of glycosylation at R5 (P = 0.0024);Gain of glycosylation at R5 (P = 0.0024);Gain of glycosylation at R5 (P = 0.0024);

MVP

0.99

MPC

0.95

ClinPred

0.81

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.15

gMVP

0.51

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over