Variant chr2-36857987-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_003162.4(STRN):c.1706C>T(p.Thr569Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000664 in 1,611,096 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

STRN
NM_003162.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.34

Variant links:

Genes affected

STRN (HGNC:11424): (striatin) Enables armadillo repeat domain binding activity; estrogen receptor binding activity; and protein phosphatase 2A binding activity. Involved in Wnt signaling pathway and negative regulation of cell population proliferation. Located in bicellular tight junction. Part of FAR/SIN/STRIPAK complex. [provided by Alliance of Genome Resources, Apr 2022]

STRN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
STRN	NM_003162.4 linkuse as main transcript	c.1706C>T	p.Thr569Met	missense_variant	14/18	ENST00000263918.9
STRN	XM_011533073.3 linkuse as main transcript	c.1793C>T	p.Thr598Met	missense_variant	15/19
STRN	XM_005264519.6 linkuse as main transcript	c.1595C>T	p.Thr532Met	missense_variant	13/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STRN	ENST00000263918.9 linkuse as main transcript	c.1706C>T	p.Thr569Met	missense_variant	14/18	1	NM_003162.4	P1	O43815-1

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000407

AC:

AN:

245498

Hom.:

AF XY:

0.0000528

AC XY:

AN XY:

132644

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:

0.000200

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000362

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000665

AC:

AN:

1459006

Hom.:

Cov.:

AF XY:

0.0000648

AC XY:

AN XY:

725576

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000451

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000140

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000702

Gnomad4 OTH exome

AF:

0.0000830

GnomAD4 genome

AF:

0.0000658

AC:

AN:

152090

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

Bravo

AF:

0.0000453

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000494

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

Jun 13, 2023

The c.1706C>T (p.T569M) alteration is located in exon 14 (coding exon 14) of the STRN gene. This alteration results from a C to T substitution at nucleotide position 1706, causing the threonine (T) at amino acid position 569 to be replaced by a methionine (M). 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

0.13

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.21

T;.

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.97

D;D

M_CAP

Benign

0.074

MetaRNN

Uncertain

0.71

D;D

MetaSVM

Uncertain

-0.14

MutationAssessor

Uncertain

2.6

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-4.3

D;D

REVEL

Uncertain

0.46

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

1.0

D;D

Vest4

0.62

MVP

0.58

MPC

0.43

ClinPred

0.79

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.31

gMVP

0.40

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