16-29664525-C-T

Position:

chr16-29664525-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003123.6(SPN):c.797C>T(p.Ala266Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 1,613,982 control chromosomes in the GnomAD database, including 168 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 7 hom., cov: 31)

Exomes 𝑓: 0.0022 ( 161 hom. )

Consequence

SPN
NM_003123.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.576

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018183589).

BP6

Variant 16-29664525-C-T is Benign according to our data. Variant chr16-29664525-C-T is described in ClinVar as [Benign]. Clinvar id is 778501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.068 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPN	NM_003123.6 linkuse as main transcript	c.797C>T	p.Ala266Val	missense_variant	2/2	ENST00000652691.1	NP_003114.1
SPN	NM_001030288.4 linkuse as main transcript	c.797C>T	p.Ala266Val	missense_variant	2/2		NP_001025459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPN	ENST00000652691.1 linkuse as main transcript	c.797C>T	p.Ala266Val	missense_variant	2/2		NM_003123.6	ENSP00000498852	P1

Frequencies

GnomAD3 genomes

AF:

0.00263

AC:

401

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0234

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:

0.000132

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.0110

AC:

2745

AN:

250424

Hom.:

142

AF XY:

0.00804

AC XY:

1090

AN XY:

135560

show subpopulations

Gnomad AFR exome

AF:

0.000556

Gnomad AMR exome

AF:

0.0783

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00524

GnomAD4 exome

AF:

0.00220

AC:

3222

AN:

1461648

Hom.:

161

Cov.:

AF XY:

0.00180

AC XY:

1306

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.0700

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.000944

GnomAD4 genome

AF:

0.00265

AC:

403

AN:

152334

Hom.:

Cov.:

AF XY:

0.00246

AC XY:

183

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000721

Gnomad4 AMR

AF:

0.0235

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000672

Hom.:

Bravo

AF:

0.00615

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00890

AC:

1081

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Jul 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.6

DANN

Benign

0.90

DEOGEN2

Benign

0.18

T;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.0072

LIST_S2

Benign

0.51

.;T;T

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.6

N;.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

1.6

N;N;N

REVEL

Benign

0.075

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.17

MPC

0.17

ClinPred

0.0036

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.022

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

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