NM_013403.3:c.56C>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_013403.3(STRN4):c.56C>A(p.Pro19Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000007 in 1,142,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000034 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000030 ( 0 hom. )

Consequence

STRN4
NM_013403.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0830

Publications

0 publications found

Variant links:

Genes affected

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:

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 Gene-Disease associations (from GenCC):

autosomal recessive limb-girdle muscular dystrophy type 2I
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, G2P, Ambry Genetics
muscular dystrophy-dystroglycanopathy type B5
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Myriad Women’s Health, Labcorp Genetics (formerly Invitae)
myopathy caused by variation in FKRP
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
congenital muscular dystrophy with cerebellar involvement
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
congenital muscular dystrophy with intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
congenital muscular dystrophy without intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
muscle-eye-brain disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
muscular dystrophy-dystroglycanopathy, type A
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

FKRP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06713852).

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STRN4	NM_013403.3 link	c.56C>A	p.Pro19Gln	missense_variant	Exon 1 of 18	ENST00000263280.11	NP_037535.2	Q9NRL3-1
FKRP	NM_024301.5 link	c.-253+285G>T		intron_variant	Intron 1 of 3	ENST00000318584.10	NP_077277.1	Q9H9S5A0A024R0R7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STRN4	ENST00000263280.11 link	c.56C>A	p.Pro19Gln	missense_variant	Exon 1 of 18	1	NM_013403.3	ENSP00000263280.4		Q9NRL3-1
FKRP	ENST00000318584.10 link	c.-253+285G>T		intron_variant	Intron 1 of 3	1	NM_024301.5	ENSP00000326570.4		Q9H9S5

Frequencies

GnomAD3 genomes

AF:

0.0000342

AC:

AN:

146320

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000496

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000635

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000301

AC:

AN:

996494

Hom.:

Cov.:

AF XY:

0.00000426

AC XY:

AN XY:

469668

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19872

American (AMR)

AF:

0.00

AC:

AN:

5686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10570

East Asian (EAS)

AF:

0.00

AC:

AN:

18268

South Asian (SAS)

AF:

0.000106

AC:

AN:

18792

European-Finnish (FIN)

AF:

0.00

AC:

AN:

16382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2468

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

866956

Other (OTH)

AF:

0.0000267

AC:

AN:

37500

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000342

AC:

AN:

146320

Hom.:

Cov.:

AF XY:

0.0000701

AC XY:

AN XY:

71282

show subpopulations

African (AFR)

AF:

0.0000496

AC:

AN:

40352

American (AMR)

AF:

0.00

AC:

AN:

14872

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3406

East Asian (EAS)

AF:

0.00

AC:

AN:

4974

South Asian (SAS)

AF:

0.000635

AC:

AN:

4726

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8958

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65840

Other (OTH)

AF:

0.00

AC:

AN:

2010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 03, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.56C>A (p.P19Q) alteration is located in exon 1 (coding exon 1) of the STRN4 gene. This alteration results from a C to A substitution at nucleotide position 56, causing the proline (P) at amino acid position 19 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.035

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.015

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0075

LIST_S2

Benign

0.54

T;T

M_CAP

Pathogenic

0.51

MetaRNN

Benign

0.067

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N

PhyloP100

0.083

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.12

N;N

REVEL

Benign

0.083

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.40

T;T

Polyphen

0.0030

B;.

Vest4

0.092

MutPred

0.16

Gain of helix (P = 0.005);Gain of helix (P = 0.005);

MVP

0.10

MPC

1.2

ClinPred

0.41

GERP RS

0.074

PromoterAI

0.042

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.16

gMVP

0.42

Mutation Taster

=94/6

polymorphism

(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.

NM_013403.3:c.56C>A

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