Genetic Variant SBSPON:p.Gly108Ser (chr8-73081106-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_153225.4(SBSPON):c.322G>A(p.Gly108Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000632 in 1,613,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00065 ( 0 hom. )

Consequence

SBSPON
NM_153225.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82

Publications

2 publications found

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 was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.08323571).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153225.4. 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
	SBSPON	NM_153225.4	MANE Select	c.322G>A	p.Gly108Ser	missense	Exon 2 of 5	NP_694957.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SBSPON	ENST00000297354.7	TSL:1 MANE Select	c.322G>A	p.Gly108Ser	missense	Exon 2 of 5	ENSP00000297354.6	Q8IVN8
SBSPON	ENST00000964790.1		c.215-9236G>A		intron	N/A	ENSP00000634849.1
SBSPON	ENST00000519697.1	TSL:2	n.690G>A		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes

AF:

0.000493

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000661

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.000391

AC:

AN:

247788

AF XY:

0.000342

show subpopulations

Gnomad AFR exome

AF:

0.000261

Gnomad AMR exome

AF:

0.000850

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000525

Gnomad OTH exome

AF:

0.000836

GnomAD4 exome

AF:

0.000646

AC:

944

AN:

1461062

Hom.:

Cov.:

AF XY:

0.000607

AC XY:

441

AN XY:

726808

show subpopulations

African (AFR)

AF:

0.000149

AC:

AN:

33458

American (AMR)

AF:

0.000852

AC:

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26116

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39672

South Asian (SAS)

AF:

0.00

AC:

AN:

86076

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53368

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000784

AC:

872

AN:

1111620

Other (OTH)

AF:

0.000431

AC:

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

104

157

209

261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000492

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41574

American (AMR)

AF:

0.00111

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000661

AC:

AN:

68030

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000569

Hom.:

Bravo

AF:

0.000499

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000501

AC:

ESP6500EA

AF:

0.000601

AC:

ExAC

AF:

0.000298

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000534

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.099

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.013

MetaRNN

Benign

0.083

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PhyloP100

3.8

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.075

Sift

Benign

0.15

Sift4G

Benign

0.16

Polyphen

0.85

Vest4

0.54

MVP

0.41

MPC

0.58

ClinPred

0.082

GERP RS

5.4

Varity_R

0.31

gMVP

0.46

Mutation Taster

=75/25

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over