chr1-153458989-A-G

Position:

• chr1-153458989-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002963.4(S100A7):​c.25T>C​(p.Ser9Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: S100A7 NM_002963.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.59

Genes affected

S100A7 (HGNC:10497): (S100 calcium binding protein A7) 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 differs from the other S100 proteins of known structure in its lack of calcium binding ability in one EF-hand at the N-terminus. The protein is overexpressed in hyperproliferative skin diseases, exhibits antimicrobial activities against bacteria and induces immunomodulatory activities. [provided by RefSeq, Nov 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3112091).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
S100A7	NM_002963.4	c.25T>C	p.Ser9Pro	missense_variant	2/3	ENST00000368723.4	NP_002954.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
S100A7	ENST00000368723.4	c.25T>C	p.Ser9Pro	missense_variant	2/3	1	NM_002963.4	ENSP00000357712.3
S100A7	ENST00000368722.5	c.25T>C	p.Ser9Pro	missense_variant	2/3	3		ENSP00000357711.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461688 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727112

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: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2024

The c.25T>C (p.S9P) alteration is located in exon 2 (coding exon 1) of the S100A7 gene. This alteration results from a T to C substitution at nucleotide position 25, causing the serine (S) at amino acid position 9 to be replaced by a proline (P). 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	0.78
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	1.9
DANN	Benign	0.97
DEOGEN2	Benign	0.11	T;T
Eigen	Benign	-0.86
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0046	N
LIST_S2	Benign	0.38	.;T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.079
Sift	Benign	0.29	T;T
Sift4G	Benign	0.21	T;T
Polyphen		0.98	D;D
Vest4		0.39
MutPred		0.37		Loss of phosphorylation at S9 (P = 0.0432);Loss of phosphorylation at S9 (P = 0.0432);
MVP		0.69
MPC		0.24
ClinPred		0.42	T
GERP RS		-4.2
Varity_R		0.90
gMVP		0.62

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

LitVar

Other links and lift over

dbSNP: rs759355639; hg19: chr1-153431465;