Variant chr16-29664607-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_003123.6(SPN):c.879C>T(p.Gly293=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0886 in 1,602,388 control chromosomes in the GnomAD database, including 11,764 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.079 ( 952 hom., cov: 31)

Exomes 𝑓: 0.090 ( 10812 hom. )

Consequence

SPN
NM_003123.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.59

Variant links:

Genes affected

SPN (HGNC:11249): (sialophorin) This gene encodes a highly sialylated glycoprotein that functions in antigen-specific activation of T cells, and is found on the surface of thymocytes, T lymphocytes, monocytes, granulocytes, and some B lymphocytes. It contains a mucin-like extracellular domain, a transmembrane region and a carboxy-terminal intracellular region. The extracellular domain has a high proportion of serine and threonine residues, allowing extensive O-glycosylation, and has one potential N-glycosylation site, while the carboxy-terminal region has potential phosphorylation sites that may mediate transduction of activation signals. Different glycoforms of this protein have been described. In stimulated immune cells, proteolytic cleavage of the extracellular domain occurs in some cell types, releasing a soluble extracellular fragment. Defects in expression of this gene are associated with Wiskott-Aldrich syndrome. [provided by RefSeq, Sep 2017]

SPN links:

QPRT (HGNC:9755): (quinolinate phosphoribosyltransferase) This gene encodes a key enzyme in catabolism of quinolinate, an intermediate in the tryptophan-nicotinamide adenine dinucleotide pathway. Quinolinate acts as a most potent endogenous exitotoxin to neurons. Elevation of quinolinate levels in the brain has been linked to the pathogenesis of neurodegenerative disorders such as epilepsy, Alzheimer's disease, and Huntington's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

QPRT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 16-29664607-C-T is Benign according to our data. Variant chr16-29664607-C-T is described in ClinVar as [Benign]. Clinvar id is 3059616.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPN	NM_003123.6 linkuse as main transcript	c.879C>T	p.Gly293=	synonymous_variant	2/2	ENST00000652691.1
SPN	NM_001030288.4 linkuse as main transcript	c.879C>T	p.Gly293=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPN	ENST00000652691.1 linkuse as main transcript	c.879C>T	p.Gly293=	synonymous_variant	2/2		NM_003123.6	P1

Frequencies

GnomAD3 genomes

AF:

0.0788

AC:

11971

AN:

151922

Hom.:

948

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0167

Gnomad AMI

AF:

0.0736

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.0963

Gnomad EAS

AF:

0.320

Gnomad SAS

AF:

0.323

Gnomad FIN

AF:

0.0866

Gnomad MID

AF:

0.0764

Gnomad NFE

AF:

0.0608

Gnomad OTH

AF:

0.0966

GnomAD3 exomes

AF:

0.142

AC:

32698

AN:

230572

Hom.:

3756

AF XY:

0.144

AC XY:

18168

AN XY:

125824

show subpopulations

Gnomad AFR exome

AF:

0.0159

Gnomad AMR exome

AF:

0.248

Gnomad ASJ exome

AF:

0.0986

Gnomad EAS exome

AF:

0.305

Gnomad SAS exome

AF:

0.313

Gnomad FIN exome

AF:

0.0902

Gnomad NFE exome

AF:

0.0658

Gnomad OTH exome

AF:

0.114

GnomAD4 exome

AF:

0.0897

AC:

130032

AN:

1450348

Hom.:

10812

Cov.:

AF XY:

0.0959

AC XY:

69170

AN XY:

720930

show subpopulations

Gnomad4 AFR exome

AF:

0.0150

Gnomad4 AMR exome

AF:

0.236

Gnomad4 ASJ exome

AF:

0.0955

Gnomad4 EAS exome

AF:

0.343

Gnomad4 SAS exome

AF:

0.310

Gnomad4 FIN exome

AF:

0.0910

Gnomad4 NFE exome

AF:

0.0598

Gnomad4 OTH exome

AF:

0.0961

GnomAD4 genome

AF:

0.0788

AC:

11979

AN:

152040

Hom.:

952

Cov.:

AF XY:

0.0851

AC XY:

6324

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.0167

Gnomad4 AMR

AF:

0.159

Gnomad4 ASJ

AF:

0.0963

Gnomad4 EAS

AF:

0.320

Gnomad4 SAS

AF:

0.322

Gnomad4 FIN

AF:

0.0866

Gnomad4 NFE

AF:

0.0608

Gnomad4 OTH

AF:

0.0960

Alfa

AF:

0.0671

Hom.:

147

Bravo

AF:

0.0792

Asia WGS

AF:

0.314

AC:

1091

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

SPN-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

6.9

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.34

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.34

Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over