1-167119270-G-C

Position:

• chr1-167119270-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001080426.3(STYXL2):​c.459G>C​(p.Gly153Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,614,246 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (32 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (35 hom.)
• Consequence: STYXL2 NM_001080426.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0470

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 Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 1-167119270-G-C is Benign according to our data. Variant chr1-167119270-G-C is described in ClinVar as [Benign]. Clinvar id is 783013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.047 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0118 (1798/152362) while in subpopulation AFR AF= 0.0414 (1723/41576). AF 95% confidence interval is 0.0398. There are 32 homozygotes in gnomad4. There are 855 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 32 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STYXL2	NM_001080426.3	c.459G>C	p.Gly153Gly	synonymous_variant	5/6	ENST00000361200.7	NP_001073895.1
STYXL2	XM_011510146.3	c.342G>C	p.Gly114Gly	synonymous_variant	4/5		XP_011508448.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STYXL2	ENST00000361200.7	c.459G>C	p.Gly153Gly	synonymous_variant	5/6	5	NM_001080426.3	ENSP00000354483.2
STYXL2	ENST00000271385.9	c.459G>C	p.Gly153Gly	synonymous_variant	5/6	1		ENSP00000271385.5
STYXL2	ENST00000443333.1	c.459G>C	p.Gly153Gly	synonymous_variant	4/5	5		ENSP00000404874.1
GPA33	ENST00000632571.1	c.-281-45731C>G		intron_variant		4		ENSP00000488407.1

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1800 AN: 152244 Hom.: 32 Cov.: 33

Gnomad AFR AF: 0.0416

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00340

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00812

GnomAD3 exomes AF: 0.00311 AC: 782 AN: 251292 Hom.: 20 AF XY: 0.00210 AC XY: 285 AN XY: 135854

Gnomad AFR exome AF: 0.0437

Gnomad AMR exome AF: 0.00148

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: 0.000123

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00122 AC: 1779 AN: 1461884 Hom.: 35 Cov.: 32 AF XY: 0.00101 AC XY: 738 AN XY: 727244

Gnomad4 AFR exome AF: 0.0415

Gnomad4 AMR exome AF: 0.00177

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000132

Gnomad4 OTH exome AF: 0.00248

GnomAD4 genome AF: 0.0118 AC: 1798 AN: 152362 Hom.: 32 Cov.: 33 AF XY: 0.0115 AC XY: 855 AN XY: 74514

Gnomad4 AFR AF: 0.0414

Gnomad4 AMR AF: 0.00340

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00803

Alfa AF: 0.000606 Hom.: 0

Bravo AF: 0.0132

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.7
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs61748776; hg19: chr1-167088507;