chr1-167117481-G-A

Position:

chr1-167117481-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001080426.3(STYXL2):c.359G>A(p.Arg120Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 1,612,296 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R120W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0029 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 16 hom. )

Consequence

STYXL2
NM_001080426.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.60

Variant links:

Genes affected

STYXL2 (HGNC:25034): (serine/threonine/tyrosine interacting like 2) Predicted to enable protein tyrosine/serine/threonine phosphatase activity. Predicted to be involved in protein dephosphorylation. Predicted to be located in sarcomere. [provided by Alliance of Genome Resources, Apr 2022]

STYXL2 links:

GPA33 (HGNC:4445): (glycoprotein A33) The glycoprotein encoded by this gene is a cell surface antigen that is expressed in greater than 95% of human colon cancers. The open reading frame encodes a 319-amino acid polypeptide having a putative secretory signal sequence and 3 potential glycosylation sites. The predicted mature protein has a 213-amino acid extracellular region, a single transmembrane domain, and a 62-amino acid intracellular tail. The sequence of the extracellular region contains 2 domains characteristic of the CD2 subgroup of the immunoglobulin (Ig) superfamily. [provided by RefSeq, Jul 2008]

GPA33 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015995622).

BP6

Variant 1-167117481-G-A is Benign according to our data. Variant chr1-167117481-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2639527.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STYXL2	NM_001080426.3 link	c.359G>A	p.Arg120Gln	missense_variant	4/6	ENST00000361200.7	NP_001073895.1	Q5VZP5
STYXL2	XM_011510146.3 link	c.242G>A	p.Arg81Gln	missense_variant	3/5		XP_011508448.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
STYXL2	ENST00000361200.7 link	c.359G>A	p.Arg120Gln	missense_variant	4/6	5	NM_001080426.3	ENSP00000354483.2	Q5VZP5
STYXL2	ENST00000271385.9 link	c.359G>A	p.Arg120Gln	missense_variant	4/6	1		ENSP00000271385.5	Q5VZP5
STYXL2	ENST00000443333.1 link	c.359G>A	p.Arg120Gln	missense_variant	3/5	5		ENSP00000404874.1	Q5VZP5
GPA33	ENST00000632571.1 link	c.-281-43942C>T		intron_variant		4		ENSP00000488407.1	A0A0J9YXH7

Frequencies

GnomAD3 genomes

AF:

0.00296

AC:

451

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.00330

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00420

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00351

AC:

867

AN:

246788

Hom.:

AF XY:

0.00378

AC XY:

504

AN XY:

133270

show subpopulations

Gnomad AFR exome

AF:

0.000252

Gnomad AMR exome

AF:

0.00169

Gnomad ASJ exome

AF:

0.000400

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00426

Gnomad FIN exome

AF:

0.00385

Gnomad NFE exome

AF:

0.00507

Gnomad OTH exome

AF:

0.00447

GnomAD4 exome

AF:

0.00336

AC:

4907

AN:

1459996

Hom.:

Cov.:

AF XY:

0.00349

AC XY:

2537

AN XY:

725984

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00195

Gnomad4 ASJ exome

AF:

0.000421

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.00521

Gnomad4 FIN exome

AF:

0.00433

Gnomad4 NFE exome

AF:

0.00351

Gnomad4 OTH exome

AF:

0.00295

GnomAD4 genome

AF:

0.00295

AC:

449

AN:

152300

Hom.:

Cov.:

AF XY:

0.00283

AC XY:

211

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.00385

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.00330

Gnomad4 NFE

AF:

0.00420

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00357

Hom.:

Bravo

AF:

0.00267

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00360

AC:

ExAC

AF:

0.00384

AC:

466

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

STYXL2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.018

T;T;T

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

.;.;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.016

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;M;M

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.5

N;N;N

REVEL

Uncertain

0.29

Sift

Uncertain

0.015

D;D;D

Sift4G

Uncertain

0.022

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.85

MVP

0.47

MPC

0.33

ClinPred

0.055

GERP RS

4.8

Varity_R

0.24

gMVP

0.80

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