chr1-153358287-A-G

Variant names:

• chr1-153358287-A-G
• rs759389626
• NM_002965.4:c.4A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002965.4(S100A9):​c.4A>G​(p.Thr2Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,441,698 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T2S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: S100A9 NM_002965.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364
• Publications: 0 publications found

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]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043462038).

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>G	p.Thr2Ala	missense	Exon 2 of 3	NP_002956.1	P06702

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100A9	ENST00000368738.4	TSL:1 MANE Select	c.4A>G	p.Thr2Ala	missense	Exon 2 of 3	ENSP00000357727.3	P06702
	S100A9	ENST00000872632.1		c.4A>G	p.Thr2Ala	missense	Exon 2 of 3	ENSP00000542691.1
	S100A9	ENST00000872634.1		c.4A>G	p.Thr2Ala	missense	Exon 1 of 2	ENSP00000542693.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1441698 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 715478

African (AFR) AF: 0.00 AC: 0 AN: 32986

American (AMR) AF: 0.00 AC: 0 AN: 42796

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25568

East Asian (EAS) AF: 0.0000509 AC: 2 AN: 39280

South Asian (SAS) AF: 0.00 AC: 0 AN: 84336

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53056

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1098548

Other (OTH) AF: 0.00 AC: 0 AN: 59446

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.051
DANN	Benign	0.22
DEOGEN2	Benign	0.17	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-2.1	N
PhyloP100		-0.36
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.49	N
REVEL	Benign	0.017
Sift	Benign	0.85	T
Sift4G	Benign	0.96	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.21		Gain of methylation at K4 (P = 0.0688)
MVP		0.25
MPC		0.48
ClinPred		0.043	T
GERP RS		-0.48
PromoterAI		-0.083	Neutral
Varity_R		0.093
gMVP		0.31
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs759389626; hg19: chr1-153330763;