1-167094920-C-T

Variant names:

• chr1-167094920-C-T
• rs199800806
• NM_001080426.3:c.71C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001080426.3(STYXL2):​c.71C>T​(p.Ala24Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000807 in 1,611,462 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 0.000013 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: STYXL2 NM_001080426.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.85
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41023546).

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.71C>T	p.Ala24Val	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.71C>T	p.Ala24Val	missense	Exon 2 of 6	ENSP00000354483.2	Q5VZP5
	STYXL2	ENST00000271385.9	TSL:1	c.71C>T	p.Ala24Val	missense	Exon 2 of 6	ENSP00000271385.5	Q5VZP5
	STYXL2	ENST00000443333.1	TSL:5	c.71C>T	p.Ala24Val	missense	Exon 1 of 5	ENSP00000404874.1	Q5VZP5

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152028 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000205 AC: 5 AN: 243940 AF XY: 0.0000303

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000587

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000181

Gnomad OTH exome AF: 0.000169

GnomAD4 exome AF: 0.00000754 AC: 11 AN: 1459434 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 725724

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.0000674 AC: 3 AN: 44478

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26062

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.0000351 AC: 3 AN: 85416

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53120

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111222

Other (OTH) AF: 0.0000166 AC: 1 AN: 60268

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152028 Hom.: 0 Cov.: 30 AF XY: 0.0000269 AC XY: 2 AN XY: 74262

African (AFR) AF: 0.0000242 AC: 1 AN: 41384

American (AMR) AF: 0.00 AC: 0 AN: 15266

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000330 AC: 4

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	Benign	0.21
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0040	T
Eigen	Benign	0.066
Eigen_PC	Benign	0.076
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		4.9
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.15
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.040	D
Polyphen		0.86	P
Vest4		0.65
MutPred		0.21		Gain of helix (P = 0.0199)
MVP		0.40
MPC		0.16
ClinPred		0.52	D
GERP RS		5.3
PromoterAI		0.00010	Neutral
Varity_R		0.11
gMVP		0.36
Mutation Taster		=98/2	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: rs199800806; hg19: chr1-167064157;