1-167117340-C-G

Variant names:

• chr1-167117340-C-G
• rs771502951
• NM_001080426.3:c.218C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080426.3(STYXL2):​c.218C>G​(p.Pro73Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P73L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STYXL2 NM_001080426.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.27
• Publications: 0 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03173268).

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.218C>G	p.Pro73Arg	missense	Exon 4 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.218C>G	p.Pro73Arg	missense	Exon 4 of 6	ENSP00000354483.2	Q5VZP5
	STYXL2	ENST00000271385.9	TSL:1	c.218C>G	p.Pro73Arg	missense	Exon 4 of 6	ENSP00000271385.5	Q5VZP5
	STYXL2	ENST00000443333.1	TSL:5	c.218C>G	p.Pro73Arg	missense	Exon 3 of 5	ENSP00000404874.1	Q5VZP5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.037
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	12
DANN	Benign	0.18
DEOGEN2	Benign	0.00076	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-2.0	N
PhyloP100		2.3
PrimateAI	Benign	0.42	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.048
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.27
MutPred		0.41		Gain of solvent accessibility (P = 3e-04)
MVP		0.13
MPC		0.046
ClinPred		0.041	T
GERP RS		0.98
Varity_R		0.026
gMVP		0.33
Mutation Taster		=100/0	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: rs771502951; hg19: chr1-167086577;