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GeneBe

1-153631835-C-G

Variant summary

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

The NM_006271.2(S100A1):c.279C>G(p.Asn93Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

S100A1
NM_006271.2 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.57
Variant links:
Genes affected
S100A1 (HGNC:10486): (S100 calcium binding protein A1) 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 stimulation of Ca2+-induced Ca2+ release, inhibition of microtubule assembly, and inhibition of protein kinase C-mediated phosphorylation. Reduced expression of this protein has been implicated in cardiomyopathies. [provided by RefSeq, Jul 2008]

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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=0.13552347).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
S100A1NM_006271.2 linkuse as main transcriptc.279C>G p.Asn93Lys missense_variant 3/3 ENST00000292169.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
S100A1ENST00000292169.6 linkuse as main transcriptc.279C>G p.Asn93Lys missense_variant 3/31 NM_006271.2 P1
ENST00000469931.2 linkuse as main transcriptn.667-10G>C splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152172
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251074
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135674
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000178
AC:
26
AN:
1461480
Hom.:
0
Cov.:
35
AF XY:
0.0000151
AC XY:
11
AN XY:
727020
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:
0.00
Gnomad4 NFE exome
AF:
0.0000216
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152172
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 GeneticsDec 27, 2023The c.279C>G (p.N93K) alteration is located in exon 3 (coding exon 2) of the S100A1 gene. This alteration results from a C to G substitution at nucleotide position 279, causing the asparagine (N) at amino acid position 93 to be replaced by a lysine (K). 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
Benign
0.17
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
Cadd
Benign
18
Dann
Uncertain
0.99
DEOGEN2
Benign
0.0051
T;T
Eigen
Benign
-0.18
Eigen_PC
Benign
-0.044
FATHMM_MKL
Benign
0.64
D
LIST_S2
Benign
0.67
T;T
M_CAP
Benign
0.041
D
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
0.56
N;N;D
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
0.12
N;N
REVEL
Benign
0.021
Sift
Uncertain
0.0050
D;T
Sift4G
Uncertain
0.0060
D;T
Polyphen
0.0010
.;B
Vest4
0.26
MutPred
0.21
.;Gain of methylation at N93 (P = 0.0038);
MVP
0.59
MPC
0.12
ClinPred
0.82
D
GERP RS
3.2
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.8
Varity_R
0.22
gMVP
0.60

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

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

Other links and lift over

dbSNP: rs1017572198; hg19: chr1-153604311; API