chr4-1167501-C-T

Variant names:

• chr4-1167501-C-T
• rs1430494473
• NM_012445.4:c.967G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012445.4(SPON2):​c.967G>A​(p.Ala323Thr) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPON2 NM_012445.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.490
• Publications: 0 publications found

Genes affected

SPON2 (HGNC:11253): (spondin 2) Predicted to enable antigen binding activity; lipopolysaccharide binding activity; and metal ion binding activity. Predicted to be involved in cell adhesion. Predicted to act upstream of or within several processes, including defense response to other organism; opsonization; and positive regulation of cytokine production. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

LOC124900647 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036288947).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012445.4. 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
	SPON2	NM_012445.4	MANE Select	c.967G>A	p.Ala323Thr	missense	Exon 6 of 6	NP_036577.2	Q9BUD6
	SPON2	NM_001128325.3		c.967G>A	p.Ala323Thr	missense	Exon 7 of 7	NP_001121797.2	Q9BUD6
	SPON2	NM_001199021.2		c.967G>A	p.Ala323Thr	missense	Exon 8 of 8	NP_001185950.2	Q9BUD6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPON2	ENST00000290902.10	TSL:1 MANE Select	c.967G>A	p.Ala323Thr	missense	Exon 6 of 6	ENSP00000290902.5	Q9BUD6
	SPON2	ENST00000960395.1		c.1291G>A	p.Ala431Thr	missense	Exon 6 of 6	ENSP00000630454.1
	SPON2	ENST00000431380.5	TSL:5	c.967G>A	p.Ala323Thr	missense	Exon 7 of 7	ENSP00000394832.1	Q9BUD6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.063
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	16
DANN	Benign	0.96
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.24	N
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.99	T
PhyloP100		0.49
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.026
Sift	Benign	0.54	T
Sift4G	Benign	0.59	T
Vest4		0.066
MutPred		0.29		Gain of catalytic residue at E322 (P = 0.5037)
MVP		0.081
MPC		0.23
ClinPred		0.12	T
GERP RS		-0.66
gMVP		0.42
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1430494473; hg19: chr4-1161289;