Variant chr19-46746181-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_013403.3(STRN4):c.250G>A(p.Ala84Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,538,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

STRN4
NM_013403.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.718

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014166921).

BS2

High AC in GnomAd4 at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STRN4	NM_013403.3 linkuse as main transcript	c.250G>A	p.Ala84Thr	missense_variant	1/18	ENST00000263280.11	NP_037535.2
FKRP	NM_024301.5 linkuse as main transcript	c.-253+91C>T		intron_variant		ENST00000318584.10	NP_077277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STRN4	ENST00000263280.11 linkuse as main transcript	c.250G>A	p.Ala84Thr	missense_variant	1/18	1	NM_013403.3	ENSP00000263280	P4	Q9NRL3-1
FKRP	ENST00000318584.10 linkuse as main transcript	c.-253+91C>T		intron_variant		1	NM_024301.5	ENSP00000326570	P1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

151480

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:

0.00124

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000133

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000308

AC:

AN:

158834

Hom.:

AF XY:

0.000243

AC XY:

AN XY:

90614

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:

0.00117

Gnomad NFE exome

AF:

0.000493

Gnomad OTH exome

AF:

0.000531

GnomAD4 exome

AF:

0.000131

AC:

182

AN:

1386678

Hom.:

Cov.:

AF XY:

0.000112

AC XY:

AN XY:

688868

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:

0.00

Gnomad4 FIN exome

AF:

0.00106

Gnomad4 NFE exome

AF:

0.000115

Gnomad4 OTH exome

AF:

0.000280

GnomAD4 genome

AF:

0.000145

AC:

AN:

151590

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74098

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:

0.00124

Gnomad4 NFE

AF:

0.000133

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000125

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.000399

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 26, 2024

The c.250G>A (p.A84T) alteration is located in exon 1 (coding exon 1) of the STRN4 gene. This alteration results from a G to A substitution at nucleotide position 250, causing the alanine (A) at amino acid position 84 to be replaced by a threonine (T). 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

0.18

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.063

T;.

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.21

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Pathogenic

0.74

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.83

L;L

MutationTaster

Benign

1.0

D;D;D;D;N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.024

Sift

Uncertain

0.0050

D;T

Sift4G

Benign

0.14

T;T

Polyphen

0.44

B;.

Vest4

0.14

MVP

0.36

MPC

0.40

ClinPred

0.077

GERP RS

0.93

Varity_R

0.18

gMVP

0.16

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over