chr11-13963052-G-T

Variant names:

• chr11-13963052-G-T
• rs781900983
• NM_006108.4:c.148G>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.148G>T​(p.Ala50Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000007 in 1,427,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A50P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SPON1 NM_006108.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.64
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1987797).

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.148G>T	p.Ala50Ser	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.148G>T	p.Ala50Ser	missense	Exon 1 of 16	ENSP00000460236.1	Q9HCB6
	SPON1	ENST00000964987.1		c.148G>T	p.Ala50Ser	missense	Exon 1 of 16	ENSP00000635046.1
	SPON1	ENST00000883678.1		c.148G>T	p.Ala50Ser	missense	Exon 1 of 15	ENSP00000553737.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1427906 Hom.: 0 Cov.: 33 AF XY: 0.00000141 AC XY: 1 AN XY: 707622

African (AFR) AF: 0.00 AC: 0 AN: 31824

American (AMR) AF: 0.00 AC: 0 AN: 40834

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25422

East Asian (EAS) AF: 0.00 AC: 0 AN: 37016

South Asian (SAS) AF: 0.00 AC: 0 AN: 80956

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1096630

Other (OTH) AF: 0.0000169 AC: 1 AN: 59142

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	0.00023	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.090	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.6
PrimateAI	Uncertain	0.54	T
Sift4G	Benign	0.11	T
Polyphen		0.26	B
Vest4		0.18
MutPred		0.60		Gain of disorder (P = 0.0169)
MVP		0.25
ClinPred		0.98	D
GERP RS		5.1
PromoterAI		0.035	Neutral
Varity_R		0.48
gMVP		0.54

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: rs781900983; hg19: chr11-13984599;