Genetic Variant NM_024301.5:c.-263_-258delGGCGGC (chr19-46746070-TGGCGGC-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_024301.5(FKRP):c.-263_-258delGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000205 in 1,216,422 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

FKRP
NM_024301.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.55

Publications

0 publications found

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:

STRN4 (HGNC:15721): (striatin 4) Enables armadillo repeat domain binding activity and protein phosphatase 2A binding activity. Part of FAR/SIN/STRIPAK complex. [provided by Alliance of Genome Resources, Apr 2022]

STRN4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP6

Variant 19-46746070-TGGCGGC-T is Benign according to our data. Variant chr19-46746070-TGGCGGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 518044.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKRP	NM_024301.5 link	c.-263_-258delGGCGGC		5_prime_UTR_variant	Exon 1 of 4	ENST00000318584.10	NP_077277.1	Q9H9S5A0A024R0R7
STRN4	NM_013403.3 link	c.282+73_282+78delGCCGCC		intron_variant	Intron 1 of 17	ENST00000263280.11	NP_037535.2	Q9NRL3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKRP	ENST00000318584.10 link	c.-263_-258delGGCGGC		5_prime_UTR_variant	Exon 1 of 4	1	NM_024301.5	ENSP00000326570.4		Q9H9S5
STRN4	ENST00000263280.11 link	c.282+73_282+78delGCCGCC		intron_variant	Intron 1 of 17	1	NM_013403.3	ENSP00000263280.4		Q9NRL3-1

Frequencies

GnomAD3 genomes

AF:

0.000120

AC:

AN:

150254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000733

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:

0.0000962

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000208

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000217

AC:

231

AN:

1066168

Hom.:

AF XY:

0.000179

AC XY:

AN XY:

518530

show subpopulations

African (AFR)

AF:

0.000104

AC:

AN:

19190

American (AMR)

AF:

0.000155

AC:

AN:

6438

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11758

East Asian (EAS)

AF:

0.00

AC:

AN:

21106

South Asian (SAS)

AF:

0.0000224

AC:

AN:

44556

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2896

European-Non Finnish (NFE)

AF:

0.000251

AC:

225

AN:

897834

Other (OTH)

AF:

0.0000488

AC:

AN:

40984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000120

AC:

AN:

150254

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

73320

show subpopulations

African (AFR)

AF:

0.0000733

AC:

AN:

40928

American (AMR)

AF:

0.00

AC:

AN:

15190

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

4968

South Asian (SAS)

AF:

0.00

AC:

AN:

4680

European-Finnish (FIN)

AF:

0.0000962

AC:

AN:

10392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.000208

AC:

AN:

67356

Other (OTH)

AF:

0.00

AC:

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.000144

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jul 21, 2017

GeneDx

Significance:Likely 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.6

Mutation Taster

=298/2

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_024301.5:c.-263_-258delGGCGGC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over