chr1-167117357-G-A

Position:

chr1-167117357-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001080426.3(STYXL2):c.235G>A(p.Ala79Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000176 in 1,611,200 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

STYXL2
NM_001080426.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.368

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.006927252).

BP6

Variant 1-167117357-G-A is Benign according to our data. Variant chr1-167117357-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3171874.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STYXL2	NM_001080426.3 link	c.235G>A	p.Ala79Thr	missense_variant	4/6	ENST00000361200.7	NP_001073895.1	Q5VZP5
STYXL2	XM_011510146.3 link	c.118G>A	p.Ala40Thr	missense_variant	3/5		XP_011508448.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
STYXL2	ENST00000361200.7 link	c.235G>A	p.Ala79Thr	missense_variant	4/6	5	NM_001080426.3	ENSP00000354483.2	Q5VZP5
STYXL2	ENST00000271385.9 link	c.235G>A	p.Ala79Thr	missense_variant	4/6	1		ENSP00000271385.5	Q5VZP5
STYXL2	ENST00000443333.1 link	c.235G>A	p.Ala79Thr	missense_variant	3/5	5		ENSP00000404874.1	Q5VZP5
GPA33	ENST00000632571.1 link	c.-281-43818C>T		intron_variant		4		ENSP00000488407.1	A0A0J9YXH7

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000392

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000139

AC:

AN:

244924

Hom.:

AF XY:

0.000121

AC XY:

AN XY:

132308

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000469

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000338

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000154

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000180

AC:

263

AN:

1458880

Hom.:

Cov.:

AF XY:

0.000165

AC XY:

120

AN XY:

725394

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.000563

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000585

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000202

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000131

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000209

Hom.:

Bravo

AF:

0.000132

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.2

DANN

Benign

0.74

DEOGEN2

Benign

0.00073

T;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.55

.;.;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.0069

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.46

N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

0.80

N;N;N

REVEL

Benign

0.0050

Sift

Benign

0.83

T;T;T

Sift4G

Benign

0.94

T;T;T

Polyphen

0.0040

B;B;B

Vest4

0.12

MVP

0.055

MPC

0.043

ClinPred

0.015

GERP RS

-5.4

Varity_R

0.020

gMVP

0.33

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