Genetic Variant S100A9:p.Thr2Ser (chr1-153358287-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002965.4(S100A9):c.4A>T(p.Thr2Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000627 in 1,594,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

S100A9
NM_002965.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.364

Publications

0 publications found

Variant links:

Genes affected

S100A9 (HGNC:10499): (S100 calcium binding protein A9) The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein may function in the inhibition of casein kinase and altered expression of this protein is associated with the disease cystic fibrosis. This antimicrobial protein exhibits antifungal and antibacterial activity. [provided by RefSeq, Nov 2014]

S100A9 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04741025).

BP6

Variant 1-153358287-A-T is Benign according to our data. Variant chr1-153358287-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2591165.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002965.4. 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
	S100A9	NM_002965.4	MANE Select	c.4A>T	p.Thr2Ser	missense	Exon 2 of 3	NP_002956.1	P06702

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
S100A9	ENST00000368738.4	TSL:1 MANE Select	c.4A>T	p.Thr2Ser	missense	Exon 2 of 3	ENSP00000357727.3	P06702
S100A9	ENST00000872632.1		c.4A>T	p.Thr2Ser	missense	Exon 2 of 3	ENSP00000542691.1
S100A9	ENST00000872634.1		c.4A>T	p.Thr2Ser	missense	Exon 1 of 2	ENSP00000542693.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000164

AC:

AN:

244508

AF XY:

0.00000755

show subpopulations

Gnomad AFR exome

AF:

0.000248

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000486

AC:

AN:

1441698

Hom.:

Cov.:

AF XY:

0.00000419

AC XY:

AN XY:

715478

show subpopulations

African (AFR)

AF:

0.000182

AC:

AN:

32986

American (AMR)

AF:

0.00

AC:

AN:

42796

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25568

East Asian (EAS)

AF:

0.00

AC:

AN:

39280

South Asian (SAS)

AF:

0.00

AC:

AN:

84336

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53056

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5682

European-Non Finnish (NFE)

AF:

9.10e-7

AC:

AN:

1098548

Other (OTH)

AF:

0.00

AC:

AN:

59446

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0000721

AC:

AN:

41582

American (AMR)

AF:

0.00

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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:

0.0000566

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.070

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.26

(source)

DANN

Benign

0.26

DEOGEN2

Benign

0.17

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.22

M_CAP

Benign

0.0026

MetaRNN

Benign

0.047

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.12

PhyloP100

-0.36

PrimateAI

Benign

0.32

PROVEAN

Benign

0.21

REVEL

Benign

0.013

Sift

Benign

0.53

Sift4G

Benign

0.80

Polyphen

0.0

Vest4

0.14

MutPred

0.22

Gain of disorder (P = 0.0752)

MVP

0.31

MPC

0.44

ClinPred

0.0047

GERP RS

-0.48

PromoterAI

-0.071

Neutral

(source)

Varity_R

0.11

gMVP

0.25

Mutation Taster

=99/1

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over