chr8-73067359-G-C

Position:

• chr8-73067359-G-C

Variant summary

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

The NM_153225.4(SBSPON):​c.777C>G​(p.His259Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000348 in 1,438,798 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: SBSPON NM_153225.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.10

Genes affected

SBSPON (HGNC:30362): (somatomedin B and thrombospondin type 1 domain containing) Predicted to be an extracellular matrix structural constituent. Colocalizes with collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

SBSPON (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SBSPON	NM_153225.4	c.777C>G	p.His259Gln	missense_variant	5/5	ENST00000297354.7	NP_694957.3
SBSPON	XM_047421408.1	c.675C>G	p.His225Gln	missense_variant	6/6		XP_047277364.1
SBSPON	XM_017013145.2	c.591C>G	p.His197Gln	missense_variant	5/5		XP_016868634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SBSPON	ENST00000297354.7	c.777C>G	p.His259Gln	missense_variant	5/5	1	NM_153225.4	ENSP00000297354.6
SBSPON	ENST00000519697.1	n.1145C>G		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000348 AC: 5 AN: 1438798 Hom.: 0 Cov.: 27 AF XY: 0.00000279 AC XY: 2 AN XY: 717428

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000458

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000378

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

Dec 03, 2024

The c.777C>G (p.H259Q) alteration is located in exon 5 (coding exon 5) of the SBSPON gene. This alteration results from a C to G substitution at nucleotide position 777, causing the histidine (H) at amino acid position 259 to be replaced by a glutamine (Q). 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	Pathogenic	0.87
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.29
Sift	Uncertain	0.0080	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.62
MutPred		0.55		Loss of disorder (P = 0.0972);
MVP		0.37
MPC		0.87
ClinPred		1.0	D
GERP RS		3.3
Varity_R		0.60
gMVP		0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs1161535199; hg19: chr8-73979594;