Genetic Variant SPP1:p.Ser105Ser (chr4-87981573-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001040058.2(SPP1):c.315G>A(p.Ser105Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,613,576 control chromosomes in the GnomAD database, including 1,816 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.062 ( 947 hom., cov: 32)

Exomes 𝑓: 0.0067 ( 869 hom. )

Consequence

SPP1
NM_001040058.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.38

Publications

5 publications found

Variant links:

Genes affected

SPP1 (HGNC:11255): (secreted phosphoprotein 1) The protein encoded by this gene is involved in the attachment of osteoclasts to the mineralized bone matrix. The encoded protein is secreted and binds hydroxyapatite with high affinity. The osteoclast vitronectin receptor is found in the cell membrane and may be involved in the binding to this protein. This protein is also a cytokine that upregulates expression of interferon-gamma and interleukin-12. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

SPP1 Gene-Disease associations (from GenCC):

systemic lupus erythematosus
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

SPP1 links:

ENSG00000286618 (HGNC:):

ENSG00000286618 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP7

Synonymous conserved (PhyloP=-3.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPP1	NM_001040058.2 link	c.315G>A	p.Ser105Ser	synonymous_variant	Exon 6 of 7	ENST00000395080.8	NP_001035147.1	P10451-1A0A024RDE2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPP1	ENST00000395080.8 link	c.315G>A	p.Ser105Ser	synonymous_variant	Exon 6 of 7	1	NM_001040058.2	ENSP00000378517.3		P10451-1

Frequencies

GnomAD3 genomes

AF:

0.0614

AC:

9324

AN:

151950

Hom.:

942

Cov.:

show subpopulations

Gnomad AFR

AF:

0.212

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0247

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000882

Gnomad OTH

AF:

0.0468

GnomAD2 exomes

AF:

0.0165

AC:

4146

AN:

251474

AF XY:

0.0121

show subpopulations

Gnomad AFR exome

AF:

0.220

Gnomad AMR exome

AF:

0.0117

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000782

Gnomad OTH exome

AF:

0.00961

GnomAD4 exome

AF:

0.00666

AC:

9727

AN:

1461508

Hom.:

869

Cov.:

AF XY:

0.00578

AC XY:

4201

AN XY:

727074

show subpopulations

African (AFR)

AF:

0.222

AC:

7420

AN:

33466

American (AMR)

AF:

0.0139

AC:

622

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000880

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000673

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.0000563

AC:

AN:

53324

Middle Eastern (MID)

AF:

0.0158

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000544

AC:

605

AN:

1111784

Other (OTH)

AF:

0.0150

AC:

904

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

477

954

1430

1907

2384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

218

436

654

872

1090

<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:

0.0615

AC:

9356

AN:

152068

Hom.:

947

Cov.:

AF XY:

0.0593

AC XY:

4412

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.213

AC:

8806

AN:

41430

American (AMR)

AF:

0.0246

AC:

377

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00145

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000882

AC:

AN:

67998

Other (OTH)

AF:

0.0464

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

372

743

1115

1486

1858

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<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:

0.0285

Hom.:

293

Bravo

AF:

0.0699

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.00164

EpiControl

AF:

0.00154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.43

(source)

DANN

Benign

0.42

PhyloP100

-3.4

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over