Variant chr1-167094935-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001080426.3(STYXL2):c.86A>G(p.Tyr29Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,454,276 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

STYXL2
NM_001080426.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.74

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STYXL2	NM_001080426.3 link	c.86A>G	p.Tyr29Cys	missense_variant	2/6	ENST00000361200.7	NP_001073895.1	Q5VZP5
STYXL2	XM_011510146.3 link	c.-8+741A>G		intron_variant			XP_011508448.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
STYXL2	ENST00000361200.7 link	c.86A>G	p.Tyr29Cys	missense_variant	2/6	5	NM_001080426.3	ENSP00000354483.2	Q5VZP5
STYXL2	ENST00000271385.9 link	c.86A>G	p.Tyr29Cys	missense_variant	2/6	1		ENSP00000271385.5	Q5VZP5
STYXL2	ENST00000443333.1 link	c.86A>G	p.Tyr29Cys	missense_variant	1/5	5		ENSP00000404874.1	Q5VZP5
GPA33	ENST00000632571.1 link	c.-281-21396T>C		intron_variant		4		ENSP00000488407.1	A0A0J9YXH7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1454276

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722520

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

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

Nov 27, 2023

The c.86A>G (p.Y29C) alteration is located in exon 1 (coding exon 1) of the DUSP27 gene. This alteration results from a A to G substitution at nucleotide position 86, causing the tyrosine (Y) at amino acid position 29 to be replaced by a cysteine (C). 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

0.76

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.054

T;T;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.91

.;.;D

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.64

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M;M

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.26

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.89

MutPred

0.30

Loss of phosphorylation at Y29 (P = 0.0297);Loss of phosphorylation at Y29 (P = 0.0297);Loss of phosphorylation at Y29 (P = 0.0297);

MVP

0.45

MPC

0.33

ClinPred

0.97

GERP RS

5.3

Varity_R

0.24

gMVP

0.58

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over