Genetic Variant S100A3:p.Thr48Asn (chr1-153547845-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002960.2(S100A3):c.143C>A(p.Thr48Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. T48S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

S100A3
NM_002960.2 missense, splice_region

Scores

Splicing: ADA: 0.0004155

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.479

Variant links:

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]

S100A3 links:

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]

S100A4 links:

LOC101928034 (HGNC:):

LOC101928034 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.07602763).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S100A3	NM_002960.2 link	c.143C>A	p.Thr48Asn	missense_variant, splice_region_variant	Exon 3 of 3	ENST00000368713.8	NP_002951.1	P33764
LOC101928034	NR_125947.1 link	n.169-576G>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
S100A3	ENST00000368713.8 link	c.143C>A	p.Thr48Asn	missense_variant, splice_region_variant	Exon 3 of 3	1	NM_002960.2	ENSP00000357702.3	P33764
S100A3	ENST00000368712.1 link	c.143C>A	p.Thr48Asn	missense_variant, splice_region_variant	Exon 3 of 3	3		ENSP00000357701.1	P33764
S100A4	ENST00000368714.1 link	c.-16+2220C>A		intron_variant	Intron 1 of 2	3		ENSP00000357703.1	P26447

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461302

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726960

show subpopulations

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:

0.0000187

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

8.7

DANN

Benign

0.92

DEOGEN2

Benign

0.027

T;T

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.65

.;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.076

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.76

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.49

N;N

REVEL

Benign

0.026

Sift

Benign

0.24

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.25

B;B

Vest4

0.20

MutPred

0.23

Loss of glycosylation at P47 (P = 0.2179);Loss of glycosylation at P47 (P = 0.2179);

MVP

0.31

MPC

0.16

ClinPred

0.30

GERP RS

-0.24

Varity_R

0.39

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00042

dbscSNV1_RF

Benign

0.0080

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over