Variant 19-46746180-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_013403.3(STRN4):c.251C>T(p.Ala84Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,385,734 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

STRN4
NM_013403.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32897192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STRN4	NM_013403.3 linkuse as main transcript	c.251C>T	p.Ala84Val	missense_variant	1/18	ENST00000263280.11	NP_037535.2
FKRP	NM_024301.5 linkuse as main transcript	c.-253+90G>A		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.251C>T	p.Ala84Val	missense_variant	1/18	1	NM_013403.3	ENSP00000263280	P4	Q9NRL3-1
FKRP	ENST00000318584.10 linkuse as main transcript	c.-253+90G>A		intron_variant		1	NM_024301.5	ENSP00000326570	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.22e-7

AC:

AN:

1385734

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

688362

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:

0.00

Gnomad4 NFE exome

AF:

9.24e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 25, 2022

The c.251C>T (p.A84V) 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 251, causing the alanine (A) at amino acid position 84 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

0.30

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;.

Eigen

Benign

0.061

Eigen_PC

Benign

0.024

FATHMM_MKL

Benign

0.37

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Pathogenic

0.88

MetaRNN

Benign

0.33

T;T

MetaSVM

Benign

-0.39

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

1.0

D;D;D;D;N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.016

D;D

Polyphen

0.61

P;.

Vest4

0.16

MutPred

0.46

Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);

MVP

0.50

MPC

0.42

ClinPred

0.87

GERP RS

3.3

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.25

gMVP

0.23

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over