Genetic Variant SBSPON:p.Ala139Thr (chr8-73071865-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_153225.4(SBSPON):c.415G>A(p.Ala139Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000999 in 1,602,116 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

SBSPON
NM_153225.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.71

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
SBSPON	NM_153225.4 link	c.415G>A	p.Ala139Thr	missense_variant	Exon 3 of 5	ENST00000297354.7	NP_694957.3	Q8IVN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBSPON	ENST00000297354.7 link	c.415G>A	p.Ala139Thr	missense_variant	Exon 3 of 5	1	NM_153225.4	ENSP00000297354.6		Q8IVN8
SBSPON	ENST00000519697.1 link	n.783G>A		non_coding_transcript_exon_variant	Exon 3 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000473

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000245

AC:

AN:

249332

Hom.:

AF XY:

0.000251

AC XY:

AN XY:

135260

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000325

Gnomad NFE exome

AF:

0.000459

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000101

AC:

146

AN:

1449996

Hom.:

Cov.:

AF XY:

0.0000886

AC XY:

AN XY:

722180

show subpopulations

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:

0.000300

Gnomad4 NFE exome

AF:

0.000114

Gnomad4 OTH exome

AF:

0.0000667

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152120

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000473

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000107

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000243

AC:

ExAC

AF:

0.000373

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 29, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.415G>A (p.A139T) alteration is located in exon 3 (coding exon 3) of the SBSPON gene. This alteration results from a G to A substitution at nucleotide position 415, causing the alanine (A) at amino acid position 139 to be replaced by a threonine (T). 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

0.71

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.88

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.84

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.63

MetaSVM

Benign

-0.77

MutationAssessor

Pathogenic

3.2

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.31

Sift

Uncertain

0.010

Sift4G

Uncertain

0.0080

Polyphen

1.0

Vest4

0.76

MVP

0.59

MPC

0.85

ClinPred

0.37

GERP RS

6.2

Varity_R

0.29

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over