chr1-167094854-C-T

Variant names:

• chr1-167094854-C-T
• rs147860718
• NM_001080426.3:c.5C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001080426.3(STYXL2):​c.5C>T​(p.Ala2Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000552 in 1,612,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000052 (0 hom.)
• Consequence: STYXL2 NM_001080426.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.85
• Publications: 2 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.099885136).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080426.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STYXL2	NM_001080426.3	MANE Select	c.5C>T	p.Ala2Val	missense	Exon 2 of 6	NP_001073895.1	Q5VZP5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STYXL2	ENST00000361200.7	TSL:5 MANE Select	c.5C>T	p.Ala2Val	missense	Exon 2 of 6	ENSP00000354483.2	Q5VZP5
	STYXL2	ENST00000271385.9	TSL:1	c.5C>T	p.Ala2Val	missense	Exon 2 of 6	ENSP00000271385.5	Q5VZP5
	STYXL2	ENST00000443333.1	TSL:5	c.5C>T	p.Ala2Val	missense	Exon 1 of 5	ENSP00000404874.1	Q5VZP5

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 13 AN: 152102 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000149 AC: 37 AN: 247746 AF XY: 0.000112

Gnomad AFR exome AF: 0.0000628

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000446

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000520 AC: 76 AN: 1460362 Hom.: 0 Cov.: 31 AF XY: 0.0000441 AC XY: 32 AN XY: 726336

African (AFR) AF: 0.0000299 AC: 1 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.000782 AC: 31 AN: 39666

South Asian (SAS) AF: 0.0000932 AC: 8 AN: 85804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000279 AC: 31 AN: 1111428

Other (OTH) AF: 0.0000829 AC: 5 AN: 60322

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152220 Hom.: 0 Cov.: 31 AF XY: 0.0000672 AC XY: 5 AN XY: 74424

African (AFR) AF: 0.0000241 AC: 1 AN: 41526

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5166

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000604

ExAC AF: 0.000132 AC: 16

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.010	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		4.9
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.64
MVP		0.52
MPC		0.31
ClinPred		0.22	T
GERP RS		5.1
PromoterAI		0.016	Neutral
Varity_R		0.22
gMVP		0.59
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs147860718; hg19: chr1-167064091; COSMIC: COSV54804535; COSMIC: COSV54804535;