NM_003123.6:c.547T>A

Variant names:

• chr16-29664275-T-A
• rs534143796
• NM_003123.6:c.547T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003123.6(SPN):​c.547T>A​(p.Ser183Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S183P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SPN NM_003123.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042381763).

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.547T>A	p.Ser183Thr	missense	Exon 2 of 2	NP_003114.1	P16150
	SPN	NM_001030288.4		c.547T>A	p.Ser183Thr	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.547T>A	p.Ser183Thr	missense	Exon 2 of 2	ENSP00000498852.1	P16150
	SPN	ENST00000360121.4	TSL:1	c.547T>A	p.Ser183Thr	missense	Exon 2 of 2	ENSP00000353238.3	P16150
	SPN	ENST00000395389.2	TSL:1	c.547T>A	p.Ser183Thr	missense	Exon 2 of 2	ENSP00000378787.2	P16150

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.87
DANN	Benign	0.38
DEOGEN2	Benign	0.25	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0046	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.13
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.090
Sift	Benign	0.18	T
Sift4G	Benign	0.54	T
Polyphen		0.0010	B
Vest4		0.027
MutPred		0.28		Loss of phosphorylation at T182 (P = 0.1131)
MVP		0.49
MPC		0.16
ClinPred		0.089	T
GERP RS		-6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.056

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: rs534143796; hg19: chr16-29675596;