Variant 14-30905532-A-G 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.1915T>C(p.Phe639Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000741 in 1,605,782 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: 𝑓 0.00049 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00077 ( 0 hom. )

Consequence

STRN3
NM_001083893.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.17

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:

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=0.0894002).

BS2

High AC in GnomAd at 75 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STRN3	NM_001083893.2 linkuse as main transcript	c.1915T>C	p.Phe639Leu	missense_variant	15/18	ENST00000357479.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRN3	ENST00000357479.10 linkuse as main transcript	c.1915T>C	p.Phe639Leu	missense_variant	15/18	5	NM_001083893.2	P3	Q13033-1
STRN3	ENST00000355683.9 linkuse as main transcript	c.1663T>C	p.Phe555Leu	missense_variant	13/16	1		A1	Q13033-2
STRN3	ENST00000555358.5 linkuse as main transcript	c.*530T>C		3_prime_UTR_variant, NMD_transcript_variant	12/15	1
STRN3	ENST00000554124.2 linkuse as main transcript	n.670T>C		non_coding_transcript_exon_variant	5/5	4

Frequencies

GnomAD3 genomes

AF:

0.000493

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000706

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000504

AC:

123

AN:

244120

Hom.:

AF XY:

0.000462

AC XY:

AN XY:

132018

show subpopulations

Gnomad AFR exome

AF:

0.0000629

Gnomad AMR exome

AF:

0.000880

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000174

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.000731

Gnomad OTH exome

AF:

0.000511

GnomAD4 exome

AF:

0.000767

AC:

1115

AN:

1453450

Hom.:

Cov.:

AF XY:

0.000745

AC XY:

538

AN XY:

722580

show subpopulations

Gnomad4 AFR exome

AF:

0.000151

Gnomad4 AMR exome

AF:

0.000970

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000108

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000915

Gnomad4 OTH exome

AF:

0.000582

GnomAD4 genome

AF:

0.000492

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000706

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000512

Hom.:

Bravo

AF:

0.000680

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000428

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3476

EpiCase

AF:

0.000664

EpiControl

AF:

0.000665

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

Sep 16, 2021

The c.1915T>C (p.F639L) alteration is located in exon 15 (coding exon 15) of the STRN3 gene. This alteration results from a T to C substitution at nucleotide position 1915, causing the phenylalanine (F) at amino acid position 639 to be replaced by a leucine (L). 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

Pathogenic

0.93

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.17

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.048

MetaRNN

Benign

0.089

T;T

MetaSVM

Uncertain

-0.093

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-4.2

D;D

REVEL

Uncertain

0.47

Sift

Benign

0.20

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.34

B;B

Vest4

0.60

MutPred

0.55

.;Gain of catalytic residue at D643 (P = 0);

MVP

0.76

MPC

0.60

ClinPred

0.066

GERP RS

5.8

Varity_R

0.36

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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