Genetic Variant FKRP:c.-270C>T (chr19-46746073-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6

The NM_024301.5(FKRP):c.-270C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000663 in 150,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FKRP
NM_024301.5 5_prime_UTR

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.171

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 -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 19-46746073-C-T is Benign according to our data. Variant chr19-46746073-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3029813.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKRP	NM_024301.5 link	c.-270C>T		5_prime_UTR_variant	Exon 1 of 4	ENST00000318584.10	NP_077277.1	Q9H9S5A0A024R0R7
STRN4	NM_013403.3 link	c.282+76G>A		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.-270C>T		5_prime_UTR_variant	Exon 1 of 4	1	NM_024301.5	ENSP00000326570.4		Q9H9S5
STRN4	ENST00000263280.11 link	c.282+76G>A		intron_variant	Intron 1 of 17	1	NM_013403.3	ENSP00000263280.4		Q9NRL3-1

Frequencies

GnomAD3 genomes

AF:

0.00000663

AC:

AN:

150908

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

999212

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

486788

African (AFR)

AF:

0.00

AC:

AN:

17600

American (AMR)

AF:

0.00

AC:

AN:

6142

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11030

East Asian (EAS)

AF:

0.00

AC:

AN:

20204

South Asian (SAS)

AF:

0.00

AC:

AN:

42504

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20128

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2744

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

840500

Other (OTH)

AF:

0.00

AC:

AN:

38360

GnomAD4 genome

AF:

0.00000663

AC:

AN:

150908

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73640

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41200

American (AMR)

AF:

0.00

AC:

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5058

South Asian (SAS)

AF:

0.00

AC:

AN:

4740

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67536

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FKRP-related disorder

Benign:1

Oct 18, 2021

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.99

PhyloP100

-0.17

PromoterAI

-0.55

Under-expression

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over