Menu
GeneBe

1-153537419-G-C

Variant summary

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

The NM_001394232.1(S100A5):c.156C>G(p.Ile52Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

S100A5
NM_001394232.1 missense

Scores

2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.44
Variant links:
Genes affected
S100A5 (HGNC:10495): (S100 calcium binding protein A5) 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 a Ca2+ affinity 20- to 100-fold higher than the other S100 proteins studied under identical conditions. This protein also binds Zn2+ and Cu2+, and Cu2+ strongly which impairs the binding of Ca2+. This protein is expressed in very restricted regions of the adult brain. [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=0.093239814).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
S100A5NM_001394232.1 linkuse as main transcriptc.156C>G p.Ile52Met missense_variant 3/3 ENST00000368717.3
LOC124904423XR_007066630.1 linkuse as main transcriptn.2996G>C non_coding_transcript_exon_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
S100A5ENST00000368717.3 linkuse as main transcriptc.156C>G p.Ile52Met missense_variant 3/33 NM_001394232.1 P1P33763-1
S100A5ENST00000368718.5 linkuse as main transcriptc.156C>G p.Ile52Met missense_variant 4/41 P1P33763-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152142
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000518
AC:
13
AN:
250920
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135674
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000231
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:
0.0000353
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000150
AC:
22
AN:
1461816
Hom.:
0
Cov.:
31
AF XY:
0.0000165
AC XY:
12
AN XY:
727212
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000201
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:
0.00000809
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152142
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000444
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000330
AC:
4

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 GeneticsJan 05, 2022The c.156C>G (p.I52M) alteration is located in exon 4 (coding exon 2) of the S100A5 gene. This alteration results from a C to G substitution at nucleotide position 156, causing the isoleucine (I) at amino acid position 52 to be replaced by a methionine (M). 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
0.10
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.55
Cadd
Benign
1.5
Dann
Uncertain
0.98
DEOGEN2
Benign
0.012
T;T
Eigen
Benign
-0.83
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.098
N
M_CAP
Benign
0.0089
T
MetaRNN
Benign
0.093
T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
0.85
D;D;D
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-1.3
N;N
REVEL
Benign
0.17
Sift
Uncertain
0.0020
D;D
Sift4G
Benign
0.076
T;T
Vest4
0.22
MutPred
0.29
Loss of stability (P = 0.0629);Loss of stability (P = 0.0629);
MVP
0.19
MPC
0.010
ClinPred
0.80
D
GERP RS
-6.2
Varity_R
0.42
gMVP
0.40

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: rs3795395; hg19: chr1-153509895; API