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GeneBe

1-153631727-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006271.2(S100A1):c.171G>T(p.Lys57Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000219 in 1,461,894 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: not found (cov: 32)
Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

S100A1
NM_006271.2 missense

Scores

8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.66
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.309058).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
S100A1NM_006271.2 linkuse as main transcriptc.171G>T p.Lys57Asn missense_variant 3/3 ENST00000292169.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
S100A1ENST00000292169.6 linkuse as main transcriptc.171G>T p.Lys57Asn missense_variant 3/31 NM_006271.2 P1
ENST00000469931.2 linkuse as main transcriptn.765C>A non_coding_transcript_exon_variant 5/55

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000478
AC:
12
AN:
250810
Hom.:
0
AF XY:
0.0000664
AC XY:
9
AN XY:
135624
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:
0.000392
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000219
AC:
32
AN:
1461894
Hom.:
0
Cov.:
34
AF XY:
0.0000316
AC XY:
23
AN XY:
727248
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:
0.000371
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
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 GeneticsNov 22, 2022The c.171G>T (p.K57N) alteration is located in exon 3 (coding exon 2) of the S100A1 gene. This alteration results from a G to T substitution at nucleotide position 171, causing the lysine (K) at amino acid position 57 to be replaced by an asparagine (N). 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
0.36
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.34
Cadd
Uncertain
24
Dann
Uncertain
1.0
DEOGEN2
Uncertain
0.48
T;D
Eigen
Benign
0.17
Eigen_PC
Uncertain
0.28
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.83
T;T
M_CAP
Benign
0.038
D
MetaRNN
Benign
0.31
T;T
MetaSVM
Benign
-0.94
T
MutationTaster
Benign
0.99
D;D;D;D
PrimateAI
Uncertain
0.68
T
PROVEAN
Uncertain
-4.0
D;D
REVEL
Benign
0.18
Sift
Uncertain
0.029
D;D
Sift4G
Benign
0.066
T;T
Polyphen
0.34
.;B
Vest4
0.44
MutPred
0.60
.;Loss of ubiquitination at K57 (P = 0.0192);
MVP
0.77
MPC
0.18
ClinPred
0.37
T
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.78
gMVP
0.61

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: rs369899959; hg19: chr1-153604203; API