rs1554907680

Variant names:

• chr11-13963064-C-T
• rs1554907680
• NM_006108.4:c.160C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006108.4(SPON1):​c.160C>T​(p.Arg54Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000351 in 1,423,726 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: SPON1 NM_006108.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.162
• 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]

LOC124902637 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.765

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.160C>T	p.Arg54Trp	missense	Exon 1 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.160C>T	p.Arg54Trp	missense	Exon 1 of 16	ENSP00000460236.1	Q9HCB6
	SPON1	ENST00000964987.1		c.160C>T	p.Arg54Trp	missense	Exon 1 of 16	ENSP00000635046.1
	SPON1	ENST00000883678.1		c.160C>T	p.Arg54Trp	missense	Exon 1 of 15	ENSP00000553737.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00 AC: 0 AN: 179710 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000351 AC: 5 AN: 1423726 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 705134

African (AFR) AF: 0.00 AC: 0 AN: 31688

American (AMR) AF: 0.00 AC: 0 AN: 40038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25338

East Asian (EAS) AF: 0.00 AC: 0 AN: 36564

South Asian (SAS) AF: 0.00 AC: 0 AN: 80466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00000457 AC: 5 AN: 1094860

Other (OTH) AF: 0.00 AC: 0 AN: 59006

GnomAD4 genome Cov.: 34

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	Pathogenic	0.78
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.96	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.16
PrimateAI	Pathogenic	0.85	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.70
MutPred		0.61		Loss of disorder (P = 0.0045)
MVP		0.46
ClinPred		0.94	D
GERP RS		5.1
PromoterAI		-0.16	Neutral
Varity_R		0.77
gMVP		0.84

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: rs1554907680; hg19: chr11-13984611;