Variant chr1-167117528-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001080426.3(STYXL2):c.406G>C(p.Glu136Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000619 in 1,455,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

STYXL2
NM_001080426.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U: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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.766

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STYXL2	NM_001080426.3 link	c.406G>C	p.Glu136Gln	missense_variant	4/6	ENST00000361200.7	NP_001073895.1	Q5VZP5
STYXL2	XM_011510146.3 link	c.289G>C	p.Glu97Gln	missense_variant	3/5		XP_011508448.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
STYXL2	ENST00000361200.7 link	c.406G>C	p.Glu136Gln	missense_variant	4/6	5	NM_001080426.3	ENSP00000354483.2	Q5VZP5
STYXL2	ENST00000271385.9 link	c.406G>C	p.Glu136Gln	missense_variant	4/6	1		ENSP00000271385.5	Q5VZP5
STYXL2	ENST00000443333.1 link	c.406G>C	p.Glu136Gln	missense_variant	3/5	5		ENSP00000404874.1	Q5VZP5
GPA33	ENST00000632571.1 link	c.-281-43989C>G		intron_variant		4		ENSP00000488407.1	A0A0J9YXH7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000169

AC:

AN:

236640

Hom.:

AF XY:

0.0000314

AC XY:

AN XY:

127504

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:

0.000141

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000619

AC:

AN:

1455056

Hom.:

Cov.:

AF XY:

0.00000968

AC XY:

AN XY:

722936

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:

0.000106

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

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

Apr 09, 2024

The c.406G>C (p.E136Q) alteration is located in exon 3 (coding exon 3) of the DUSP27 gene. This alteration results from a G to C substitution at nucleotide position 406, causing the glutamic acid (E) at amino acid position 136 to be replaced by a glutamine (Q). 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

Uncertain

0.41

BayesDel_addAF

Benign

-0.084

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

T;T;T

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

.;.;D

M_CAP

Benign

0.024

MetaRNN

Pathogenic

0.77

D;D;D

MetaSVM

Benign

-0.46

MutationAssessor

Uncertain

2.1

M;M;M

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.27

Sift

Uncertain

0.028

D;D;D

Sift4G

Uncertain

0.018

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.81

MutPred

0.54

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MVP

0.66

MPC

0.31

ClinPred

0.73

GERP RS

4.9

Varity_R

0.34

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.23

Position offset: 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