NM_006108.4:c.2199G>T

Variant names:

• chr11-14262914-G-T
• rs1554942068
• NM_006108.4:c.2199G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006108.4(SPON1):​c.2199G>T​(p.Glu733Asp) 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. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SPON1 NM_006108.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.77
• 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]

SPON1-AS1 (HGNC:53117): (SPON1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21558279).

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.2199G>T	p.Glu733Asp	missense	Exon 15 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.2199G>T	p.Glu733Asp	missense	Exon 15 of 16	ENSP00000460236.1	Q9HCB6
	SPON1	ENST00000964987.1		c.2163G>T	p.Glu721Asp	missense	Exon 15 of 16	ENSP00000635046.1
	SPON1	ENST00000883678.1		c.2058G>T	p.Glu686Asp	missense	Exon 14 of 15	ENSP00000553737.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

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	0.082
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Benign	0.88
DEOGEN2	Benign	0.085	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.074
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.63	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.8
PrimateAI	Benign	0.48	T
Sift4G	Benign	0.20	T
Polyphen		0.0070	B
Vest4		0.57
MutPred		0.22		Loss of ubiquitination at K728 (P = 0.0982)
MVP		0.32
ClinPred		0.98	D
GERP RS		4.2
Varity_R		0.41
gMVP		0.43
Mutation Taster		=99/1	polymorphism

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: rs1554942068; hg19: chr11-14284460;