1-167117492-C-G

Position:

• chr1-167117492-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001080426.3(STYXL2):​c.370C>G​(p.Gln124Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STYXL2 NM_001080426.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.54

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29744902).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STYXL2	NM_001080426.3	c.370C>G	p.Gln124Glu	missense_variant	4/6	ENST00000361200.7	NP_001073895.1
STYXL2	XM_011510146.3	c.253C>G	p.Gln85Glu	missense_variant	3/5		XP_011508448.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STYXL2	ENST00000361200.7	c.370C>G	p.Gln124Glu	missense_variant	4/6	5	NM_001080426.3	ENSP00000354483.2
STYXL2	ENST00000271385.9	c.370C>G	p.Gln124Glu	missense_variant	4/6	1		ENSP00000271385.5
STYXL2	ENST00000443333.1	c.370C>G	p.Gln124Glu	missense_variant	3/5	5		ENSP00000404874.1
GPA33	ENST00000632571.1	c.-281-43953G>C		intron_variant		4		ENSP00000488407.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2023

The c.370C>G (p.Q124E) alteration is located in exon 3 (coding exon 3) of the DUSP27 gene. This alteration results from a C to G substitution at nucleotide position 370, causing the glutamine (Q) at amino acid position 124 to be replaced by a glutamic acid (E). 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	Benign	0.079
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0029	T;T;T
Eigen	Benign	-0.014
Eigen_PC	Benign	0.038
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.87	.;.;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.9	L;L;L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.55	N;N;N
REVEL	Benign	0.072
Sift	Uncertain	0.0090	D;D;D
Sift4G	Uncertain	0.052	T;T;T
Polyphen		0.69	P;P;P
Vest4		0.52
MutPred		0.34		Gain of disorder (P = 0.1364);Gain of disorder (P = 0.1364);Gain of disorder (P = 0.1364);
MVP		0.14
MPC		0.075
ClinPred		0.43	T
GERP RS		4.9
Varity_R		0.12
gMVP		0.72

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.

Other links and lift over

hg19: chr1-167086729;