1-153547699-G-C

Variant names:

• chr1-153547699-G-C
• rs571596892
• NM_002960.2:c.289C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002960.2(S100A3):​c.289C>G​(p.Pro97Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P97S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: S100A3 NM_002960.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.22

Genes affected

S100A3 (HGNC:10493): (S100 calcium binding protein A3) 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 has the highest content of cysteines of all S100 proteins, has a high affinity for Zinc, and is highly expressed in human hair cuticle. The precise function of this protein is unknown. [provided by RefSeq, Jul 2008]

S100A4 (HGNC:10494): (S100 calcium binding protein A4) 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 motility, invasion, and tubulin polymerization. Chromosomal rearrangements and altered expression of this gene have been implicated in tumor metastasis. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

LOC101928034 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.116551906).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S100A3	NM_002960.2	c.289C>G	p.Pro97Ala	missense_variant	Exon 3 of 3	ENST00000368713.8	NP_002951.1
LOC101928034	NR_125947.1	n.169-722G>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
S100A3	ENST00000368713.8	c.289C>G	p.Pro97Ala	missense_variant	Exon 3 of 3	1	NM_002960.2	ENSP00000357702.3
S100A3	ENST00000368712.1	c.289C>G	p.Pro97Ala	missense_variant	Exon 3 of 3	3		ENSP00000357701.1
S100A4	ENST00000368714.1	c.-16+2366C>G		intron_variant	Intron 1 of 2	3		ENSP00000357703.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.011	T;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.46	.;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.10
Sift	Benign	0.036	D;D
Sift4G	Benign	0.12	T;T
Polyphen		0.029	B;B
Vest4		0.16
MutPred		0.38		Loss of glycosylation at P97 (P = 0.0126);Loss of glycosylation at P97 (P = 0.0126);
MVP		0.32
MPC		0.054
ClinPred		0.22	T
GERP RS		4.1
Varity_R		0.13
gMVP		0.086

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: rs571596892; hg19: chr1-153520175;