4-1170500-C-T

Position:

• chr4-1170500-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012445.4(SPON2):​c.713G>A​(p.Arg238Lys) 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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: SPON2 NM_012445.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0220

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12662324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPON2	NM_012445.4	c.713G>A	p.Arg238Lys	missense_variant	5/6	ENST00000290902.10	NP_036577.2
SPON2	NM_001128325.3	c.713G>A	p.Arg238Lys	missense_variant	6/7		NP_001121797.2
SPON2	NM_001199021.2	c.713G>A	p.Arg238Lys	missense_variant	7/8		NP_001185950.2
LOC124900647	XM_047416477.1	c.-2486-20600C>T		intron_variant			XP_047272433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPON2	ENST00000290902.10	c.713G>A	p.Arg238Lys	missense_variant	5/6	1	NM_012445.4	ENSP00000290902.5
SPON2	ENST00000431380.5	c.713G>A	p.Arg238Lys	missense_variant	6/7	5		ENSP00000394832.1
SPON2	ENST00000617421.4	c.713G>A	p.Arg238Lys	missense_variant	7/8	5		ENSP00000483599.1
SPON2	ENST00000509697.1	n.149G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 39

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

Mar 07, 2024

The c.713G>A (p.R238K) alteration is located in exon 7 (coding exon 4) of the SPON2 gene. This alteration results from a G to A substitution at nucleotide position 713, causing the arginine (R) at amino acid position 238 to be replaced by a lysine (K). 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	Benign	0.077
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.6
DANN	Benign	0.92
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.17	N
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.93	T
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.23	N;N;.
REVEL	Benign	0.064
Sift	Benign	0.99	T;T;.
Sift4G	Benign	0.94	T;T;T
Vest4		0.093
MutPred		0.48		Gain of glycosylation at T240 (P = 0.0266);Gain of glycosylation at T240 (P = 0.0266);Gain of glycosylation at T240 (P = 0.0266);
MVP		0.21
MPC		0.24
ClinPred		0.27	T
GERP RS		2.3
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: chr4-1164288;