rs11574556

Variant names:

• chr16-29664403-C-G
• rs11574556
• NM_003123.6:c.675C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-29664403-C-G
• chr16-29664403-C-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_003123.6(SPN):​c.675C>G​(p.Ser225Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00367 in 1,614,184 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. S225S) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0028 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0038 (8 hom.)
• Consequence: SPN NM_003123.6 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.12
• Publications: 3 publications found

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]

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]

ENSG00000305172 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004766196).
• BP6: Variant 16-29664403-C-G is Benign according to our data. Variant chr16-29664403-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3037910.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003123.6. 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
	SPN	NM_003123.6	MANE Select	c.675C>G	p.Ser225Arg	missense	Exon 2 of 2	NP_003114.1	P16150
	SPN	NM_001030288.4		c.675C>G	p.Ser225Arg	missense	Exon 2 of 2	NP_001025459.1	P16150

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPN	ENST00000652691.1	MANE Select	c.675C>G	p.Ser225Arg	missense	Exon 2 of 2	ENSP00000498852.1	P16150
	SPN	ENST00000360121.4	TSL:1	c.675C>G	p.Ser225Arg	missense	Exon 2 of 2	ENSP00000353238.3	P16150
	SPN	ENST00000395389.2	TSL:1	c.675C>G	p.Ser225Arg	missense	Exon 2 of 2	ENSP00000378787.2	P16150

Frequencies

GnomAD3 genomes AF: 0.00281 AC: 428 AN: 152200 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00694

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00378

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00238 AC: 598 AN: 251422 AF XY: 0.00233

Gnomad AFR exome AF: 0.000984

Gnomad AMR exome AF: 0.00387

Gnomad ASJ exome AF: 0.000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00365

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00376 AC: 5492 AN: 1461866 Hom.: 8 Cov.: 31 AF XY: 0.00368 AC XY: 2675 AN XY: 727232

African (AFR) AF: 0.000568 AC: 19 AN: 33480

American (AMR) AF: 0.00425 AC: 190 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00172 AC: 45 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.000206 AC: 11 AN: 53394

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.00446 AC: 4963 AN: 1112010

Other (OTH) AF: 0.00426 AC: 257 AN: 60396

GnomAD4 genome AF: 0.00281 AC: 428 AN: 152318 Hom.: 0 Cov.: 31 AF XY: 0.00271 AC XY: 202 AN XY: 74482

African (AFR) AF: 0.00111 AC: 46 AN: 41580

American (AMR) AF: 0.00693 AC: 106 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00378 AC: 257 AN: 68034

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.000464 Hom.: 3

Bravo AF: 0.00303

TwinsUK AF: 0.00485 AC: 18

ALSPAC AF: 0.00285 AC: 11

ExAC AF: 0.00198 AC: 240

EpiCase AF: 0.00311

EpiControl AF: 0.00397

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SPN-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.10
DANN	Benign	0.67
DEOGEN2	Benign	0.32	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0065	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.5	L
PhyloP100		-1.1
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.12
Sift	Benign	0.32	T
Sift4G	Benign	0.26	T
Polyphen		0.013	B
Vest4		0.11
MutPred		0.22		Gain of MoRF binding (P = 0.0148)
MVP		0.50
MPC		0.71
ClinPred		0.0065	T
GERP RS		-3.9
Varity_R		0.087
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs11574556; hg19: chr16-29675724; COSMIC: COSV64070501; COSMIC: COSV64070501;