Variant 19-46755524-C-T 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.74C>T(p.Ser25Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,610,028 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: 0.0000048 ( 0 hom. )

Consequence

FKRP
NM_024301.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.38

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 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 link	c.74C>T	p.Ser25Leu	missense_variant	4/4	ENST00000318584.10	NP_077277.1	Q9H9S5A0A024R0R7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FKRP	ENST00000318584.10 link	c.74C>T	p.Ser25Leu	missense_variant	4/4	1	NM_024301.5	ENSP00000326570.4		Q9H9S5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000836

AC:

AN:

239162

Hom.:

AF XY:

0.00

AC XY:

AN XY:

130738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000187

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1457786

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724972

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000826

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

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

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.82

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

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.44

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

MetaSVM

Pathogenic

1.1

MutationAssessor

Benign

1.6

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

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.38

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

REVEL

Uncertain

0.58

Sift

Benign

0.38

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

Sift4G

Pathogenic

0.0

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

Polyphen

0.98

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

Vest4

0.29, 0.23

MutPred

0.40

Loss of disorder (P = 0.0676);Loss of disorder (P = 0.0676);Loss of disorder (P = 0.0676);Loss of disorder (P = 0.0676);Loss of disorder (P = 0.0676);Loss of disorder (P = 0.0676);Loss of disorder (P = 0.0676);Loss of disorder (P = 0.0676);Loss of disorder (P = 0.0676);Loss of disorder (P = 0.0676);Loss of disorder (P = 0.0676);Loss of disorder (P = 0.0676);Loss of disorder (P = 0.0676);Loss of disorder (P = 0.0676);Loss of disorder (P = 0.0676);Loss of disorder (P = 0.0676);Loss of disorder (P = 0.0676);

MVP

0.97

MPC

1.5

ClinPred

0.55

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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