11-13963136-T-A

Position:

• chr11-13963136-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006108.4(SPON1):​c.232T>A​(p.Tyr78Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: SPON1 NM_006108.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.06

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]

LOC124902637 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.914

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPON1	NM_006108.4	c.232T>A	p.Tyr78Asn	missense_variant	1/16	ENST00000576479.4
LOC124902637	XR_007062602.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPON1	ENST00000576479.4	c.232T>A	p.Tyr78Asn	missense_variant	1/16	1	NM_006108.4	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 27, 2022

The c.232T>A (p.Y78N) alteration is located in exon 1 (coding exon 1) of the SPON1 gene. This alteration results from a T to A substitution at nucleotide position 232, causing the tyrosine (Y) at amino acid position 78 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.54	D
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.81	T
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	-0.091	T
MutationAssessor	Pathogenic	3.2	M
PrimateAI	Uncertain	0.74	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.94
MutPred		0.74		Loss of phosphorylation at Y78 (P = 0.0309);
MVP		0.42
ClinPred		1.0	D
GERP RS		4.0
Varity_R		0.82
gMVP		0.94

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-13984683;