19-46746390-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013403.3(STRN4):​c.41C>T​(p.Ala14Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000319 in 939,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A14G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000032 ( 0 hom. )

Consequence

STRN4
NM_013403.3 missense

Scores

2
1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.317

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]
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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13950333).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STRN4NM_013403.3 linkc.41C>T p.Ala14Val missense_variant Exon 1 of 18 ENST00000263280.11 NP_037535.2 Q9NRL3-1
FKRPNM_024301.5 linkc.-253+300G>A 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
STRN4ENST00000263280.11 linkc.41C>T p.Ala14Val missense_variant Exon 1 of 18 1 NM_013403.3 ENSP00000263280.4 Q9NRL3-1
FKRPENST00000318584.10 linkc.-253+300G>A intron_variant Intron 1 of 3 1 NM_024301.5 ENSP00000326570.4 Q9H9S5

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
AF:
0.00000319
AC:
3
AN:
939684
Hom.:
0
Cov.:
33
AF XY:
0.00000680
AC XY:
3
AN XY:
441128
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
18358
American (AMR)
AF:
0.00
AC:
0
AN:
4222
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
8562
East Asian (EAS)
AF:
0.00
AC:
0
AN:
11926
South Asian (SAS)
AF:
0.00
AC:
0
AN:
18204
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10768
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2194
European-Non Finnish (NFE)
AF:
0.00000241
AC:
2
AN:
831594
Other (OTH)
AF:
0.0000295
AC:
1
AN:
33856
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.442
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
30
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 04, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.41C>T (p.A14V) alteration is located in exon 1 (coding exon 1) of the STRN4 gene. This alteration results from a C to T substitution at nucleotide position 41, causing the alanine (A) at amino acid position 14 to be replaced by a valine (V). 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
0.21
BayesDel_addAF
Benign
-0.036
T
BayesDel_noAF
Benign
-0.29
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.024
T;.
Eigen
Benign
-0.89
Eigen_PC
Benign
-0.90
FATHMM_MKL
Benign
0.067
N
LIST_S2
Benign
0.57
T;T
M_CAP
Pathogenic
0.55
D
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.55
N;N
PhyloP100
0.32
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-0.36
N;N
REVEL
Benign
0.042
Sift
Benign
0.051
T;T
Sift4G
Benign
0.27
T;T
Polyphen
0.20
B;.
Vest4
0.15
MutPred
0.20
Gain of MoRF binding (P = 0.0911);Gain of MoRF binding (P = 0.0911);
MVP
0.29
MPC
0.95
ClinPred
0.70
D
GERP RS
1.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.1
Varity_R
0.076
gMVP
0.38
Mutation Taster
=92/8
polymorphism

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

Other links and lift over

dbSNP: rs1027043038; hg19: chr19-47249647; API