11-13963004-C-G

Variant names:

• chr11-13963004-C-G
• rs373585962
• NM_006108.4:c.100C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006108.4(SPON1):​c.100C>G​(p.Leu34Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000188 in 1,594,556 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00079 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: SPON1 NM_006108.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.374
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007828414).

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.100C>G	p.Leu34Val	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.100C>G	p.Leu34Val	missense	Exon 1 of 16	ENSP00000460236.1	Q9HCB6
	SPON1	ENST00000964987.1		c.100C>G	p.Leu34Val	missense	Exon 1 of 16	ENSP00000635046.1
	SPON1	ENST00000883678.1		c.100C>G	p.Leu34Val	missense	Exon 1 of 15	ENSP00000553737.1

Frequencies

GnomAD3 genomes AF: 0.000788 AC: 120 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00272

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000157 AC: 33 AN: 209882 AF XY: 0.0000951

Gnomad AFR exome AF: 0.00196

Gnomad AMR exome AF: 0.000283

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000325

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000125 AC: 180 AN: 1442216 Hom.: 1 Cov.: 31 AF XY: 0.000138 AC XY: 99 AN XY: 716068

African (AFR) AF: 0.00277 AC: 90 AN: 32546

American (AMR) AF: 0.000304 AC: 13 AN: 42828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25710

East Asian (EAS) AF: 0.00 AC: 0 AN: 38312

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50790

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5742

European-Non Finnish (NFE) AF: 0.0000607 AC: 67 AN: 1103650

Other (OTH) AF: 0.000134 AC: 8 AN: 59614

GnomAD4 genome AF: 0.000788 AC: 120 AN: 152340 Hom.: 0 Cov.: 33 AF XY: 0.000832 AC XY: 62 AN XY: 74494

African (AFR) AF: 0.00272 AC: 113 AN: 41592

American (AMR) AF: 0.000261 AC: 4 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000405 Hom.: 0

Bravo AF: 0.000990

ESP6500AA AF: 0.00126 AC: 5

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000117 AC: 14

Asia WGS AF: 0.000289 AC: 1 AN: 3474

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	0.060
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.074	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.087
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.0078	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.41	N
PhyloP100		0.37
PrimateAI	Uncertain	0.70	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.15
MVP		0.36
ClinPred		0.072	T
GERP RS		5.2
PromoterAI		0.015	Neutral
Varity_R		0.17
gMVP		0.31

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: rs373585962; hg19: chr11-13984551;