NM_006108.4:c.461C>T

Variant names:

• chr11-14041636-C-T
• rs1247881041
• NM_006108.4:c.461C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006108.4(SPON1):​c.461C>T​(p.Thr154Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPON1 NM_006108.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.57
• Publications: 0 publications found

Genes affected

SPON1 (HGNC:11252): (spondin 1) Predicted to be an extracellular matrix structural constituent. Predicted to be involved in cell adhesion. Predicted to act upstream of or within positive regulation of protein binding activity; positive regulation of protein processing; and regulation of amyloid precursor protein catabolic process. Located in extracellular space. Colocalizes with collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006108.4. 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
	SPON1	NM_006108.4	MANE Select	c.461C>T	p.Thr154Ile	missense	Exon 3 of 16	NP_006099.2	Q9HCB6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPON1	ENST00000576479.4	TSL:1 MANE Select	c.461C>T	p.Thr154Ile	missense	Exon 3 of 16	ENSP00000460236.1	Q9HCB6
	SPON1	ENST00000964987.1		c.461C>T	p.Thr154Ile	missense	Exon 3 of 16	ENSP00000635046.1
	SPON1	ENST00000883678.1		c.461C>T	p.Thr154Ile	missense	Exon 3 of 15	ENSP00000553737.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.6
PrimateAI	Uncertain	0.78	T
Sift4G	Uncertain	0.055	T
Polyphen		0.93	P
Vest4		0.69
MutPred		0.62		Gain of catalytic residue at L159 (P = 0.0468)
MVP		0.31
ClinPred		0.93	D
GERP RS		5.0
Varity_R		0.65
gMVP		0.79

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: rs1247881041; hg19: chr11-14063183;