Variant chr14-30918974-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001083893.2(STRN3):c.1232C>T(p.Ala411Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000042 in 1,428,616 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: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

STRN3
NM_001083893.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.99

Variant links:

Genes affected

STRN3 (HGNC:15720): (striatin 3) Enables armadillo repeat domain binding activity; protein phosphatase 2A binding activity; and small GTPase binding activity. Involved in negative regulation of transcription by RNA polymerase II and positive regulation of transcription by RNA polymerase II. Located in Golgi apparatus; nucleoplasm; and plasma membrane. Part of FAR/SIN/STRIPAK complex. [provided by Alliance of Genome Resources, Apr 2022]

STRN3 links:

STRN3 (HGNC:):

STRN3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26225737).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STRN3	NM_001083893.2 linkuse as main transcript	c.1232C>T	p.Ala411Val	missense_variant	9/18	ENST00000357479.10	NP_001077362.1	Q13033-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STRN3	ENST00000357479.10 linkuse as main transcript	c.1232C>T	p.Ala411Val	missense_variant	9/18	5	NM_001083893.2	ENSP00000350071.5		Q13033-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000863

AC:

AN:

231832

Hom.:

AF XY:

0.0000159

AC XY:

AN XY:

126176

show subpopulations

Gnomad AFR exome

AF:

0.0000703

Gnomad AMR exome

AF:

0.0000331

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000420

AC:

AN:

1428616

Hom.:

Cov.:

AF XY:

0.00000704

AC XY:

AN XY:

710488

show subpopulations

Gnomad4 AFR exome

AF:

0.0000312

Gnomad4 AMR exome

AF:

0.0000485

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000123

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000183

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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 31, 2022

The c.1232C>T (p.A411V) alteration is located in exon 9 (coding exon 9) of the STRN3 gene. This alteration results from a C to T substitution at nucleotide position 1232, causing the alanine (A) at amino acid position 411 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

0.086

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

T;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.0079

MetaRNN

Benign

0.26

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.49

N;.

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.23

N;N

REVEL

Benign

0.17

Sift

Benign

0.099

T;D

Sift4G

Benign

0.29

T;T

Polyphen

0.99

D;.

Vest4

0.56

MutPred

0.41

Gain of catalytic residue at E415 (P = 0.0111);.;

MVP

0.56

MPC

0.12

ClinPred

0.41

GERP RS

4.5

Varity_R

0.12

gMVP

0.35

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