1-167117484-C-A

Variant summary

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

The NM_001080426.3(STYXL2):​c.362C>A​(p.Ala121Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000546 in 1,612,114 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

STYXL2
NM_001080426.3 missense

Scores

1
11
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.61
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]
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]

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 rank MANE Protein UniProt
STYXL2NM_001080426.3 linkc.362C>A p.Ala121Asp missense_variant Exon 4 of 6 ENST00000361200.7 NP_001073895.1 Q5VZP5
STYXL2XM_011510146.3 linkc.245C>A p.Ala82Asp missense_variant Exon 3 of 5 XP_011508448.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STYXL2ENST00000361200.7 linkc.362C>A p.Ala121Asp missense_variant Exon 4 of 6 5 NM_001080426.3 ENSP00000354483.2 Q5VZP5
STYXL2ENST00000271385.9 linkc.362C>A p.Ala121Asp missense_variant Exon 4 of 6 1 ENSP00000271385.5 Q5VZP5
STYXL2ENST00000443333.1 linkc.362C>A p.Ala121Asp missense_variant Exon 3 of 5 5 ENSP00000404874.1 Q5VZP5
GPA33ENST00000632571.1 linkc.-281-43945G>T intron_variant Intron 1 of 3 4 ENSP00000488407.1 A0A0J9YXH7

Frequencies

GnomAD3 genomes
AF:
0.000283
AC:
43
AN:
152198
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000893
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000393
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000851
AC:
21
AN:
246688
Hom.:
0
AF XY:
0.0000375
AC XY:
5
AN XY:
133222
show subpopulations
Gnomad AFR exome
AF:
0.000942
Gnomad AMR exome
AF:
0.000146
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.0000308
AC:
45
AN:
1459916
Hom.:
0
Cov.:
31
AF XY:
0.0000234
AC XY:
17
AN XY:
725926
show subpopulations
Gnomad4 AFR exome
AF:
0.000927
Gnomad4 AMR exome
AF:
0.000180
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:
0.0000331
GnomAD4 genome
AF:
0.000283
AC:
43
AN:
152198
Hom.:
0
Cov.:
33
AF XY:
0.000309
AC XY:
23
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.000893
Gnomad4 AMR
AF:
0.000393
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000378
Hom.:
0
Bravo
AF:
0.000412
ESP6500AA
AF:
0.000908
AC:
4
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000123
AC:
15

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 22, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.362C>A (p.A121D) alteration is located in exon 3 (coding exon 3) of the DUSP27 gene. This alteration results from a C to A substitution at nucleotide position 362, causing the alanine (A) at amino acid position 121 to be replaced by an aspartic acid (D). 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
0.63
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Uncertain
0.0
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.015
T;T;T
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.88
.;.;D
M_CAP
Benign
0.031
D
MetaRNN
Uncertain
0.48
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
M;M;M
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-1.7
N;N;N
REVEL
Benign
0.25
Sift
Uncertain
0.010
D;D;D
Sift4G
Uncertain
0.0090
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.87
MVP
0.51
MPC
0.20
ClinPred
0.069
T
GERP RS
4.8
Varity_R
0.28
gMVP
0.92

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.

Other links and lift over

dbSNP: rs148991366; hg19: chr1-167086721; API