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GeneBe

1-153548449-C-A

Variant summary

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

The NM_002960.2(S100A3):c.37G>T(p.Val13Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000142 in 1,608,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

S100A3
NM_002960.2 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.107
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]
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]

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=0.116022855).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
S100A3NM_002960.2 linkuse as main transcriptc.37G>T p.Val13Leu missense_variant 2/3 ENST00000368713.8
LOC101928034NR_125947.1 linkuse as main transcriptn.197C>A non_coding_transcript_exon_variant 2/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
S100A3ENST00000368713.8 linkuse as main transcriptc.37G>T p.Val13Leu missense_variant 2/31 NM_002960.2 P1
S100A3ENST00000368712.1 linkuse as main transcriptc.37G>T p.Val13Leu missense_variant 2/33 P1
S100A4ENST00000368714.1 linkuse as main transcriptc.-16+1616G>T intron_variant 3 P1

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152146
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000805
AC:
20
AN:
248468
Hom.:
0
AF XY:
0.0000894
AC XY:
12
AN XY:
134244
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000472
Gnomad NFE exome
AF:
0.000143
Gnomad OTH exome
AF:
0.000331
GnomAD4 exome
AF:
0.000151
AC:
220
AN:
1456472
Hom.:
0
Cov.:
32
AF XY:
0.000129
AC XY:
93
AN XY:
723720
show subpopulations
Gnomad4 AFR exome
AF:
0.0000898
Gnomad4 AMR exome
AF:
0.0000225
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:
0.000181
Gnomad4 OTH exome
AF:
0.000249
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
152146
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74312
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000995
Hom.:
0
Bravo
AF:
0.0000869
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000659
AC:
8

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 29, 2022The c.37G>T (p.V13L) alteration is located in exon 2 (coding exon 1) of the S100A3 gene. This alteration results from a G to T substitution at nucleotide position 37, causing the valine (V) at amino acid position 13 to be replaced by a leucine (L). 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
Uncertain
0.35
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.65
Cadd
Benign
16
Dann
Benign
0.86
DEOGEN2
Benign
0.044
T;T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.074
N
M_CAP
Benign
0.0034
T
MetaRNN
Benign
0.12
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.2
L;L
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-1.6
N;N
REVEL
Benign
0.024
Sift
Benign
0.069
T;T
Sift4G
Benign
0.065
T;T
Polyphen
0.0060
B;B
Vest4
0.29
MutPred
0.68
Loss of catalytic residue at V13 (P = 0.2079);Loss of catalytic residue at V13 (P = 0.2079);
MVP
0.13
MPC
0.057
ClinPred
0.030
T
GERP RS
0.16
Varity_R
0.29
gMVP
0.27

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.30
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.30
Position offset: -15

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200355997; hg19: chr1-153520925; API