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GeneBe

1-153543860-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_002961.3(S100A4):c.205G>A(p.Glu69Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,614,066 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

S100A4
NM_002961.3 missense

Scores

1
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.24
Variant links:
Genes affected
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1
In a binding_site (size 0) in uniprot entity S10A4_HUMAN
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
S100A4NM_002961.3 linkuse as main transcriptc.205G>A p.Glu69Lys missense_variant 3/3 ENST00000368716.9
S100A4NM_019554.3 linkuse as main transcriptc.205G>A p.Glu69Lys missense_variant 4/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
S100A4ENST00000368716.9 linkuse as main transcriptc.205G>A p.Glu69Lys missense_variant 3/31 NM_002961.3 P1

Frequencies

GnomAD3 genomes
AF:
0.0000788
AC:
12
AN:
152192
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
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:
0.0000278
AC:
7
AN:
251492
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000217
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000198
AC:
29
AN:
1461874
Hom.:
0
Cov.:
31
AF XY:
0.0000220
AC XY:
16
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.000239
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000378
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152192
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.000217
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000141
Hom.:
0
Bravo
AF:
0.000147
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 GeneticsOct 12, 2021The c.205G>A (p.E69K) alteration is located in exon 4 (coding exon 2) of the S100A4 gene. This alteration results from a G to A substitution at nucleotide position 205, causing the glutamic acid (E) at amino acid position 69 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
Pathogenic
0.73
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.40
Cadd
Uncertain
25
Dann
Uncertain
1.0
DEOGEN2
Uncertain
0.73
D;D;D;D
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Uncertain
0.83
D
M_CAP
Benign
0.0082
T
MetaRNN
Uncertain
0.52
D;D;D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
L;L;L;L
MutationTaster
Benign
0.97
D;D;D;D
PrimateAI
Uncertain
0.62
T
PROVEAN
Uncertain
-2.9
D;D;D;D
REVEL
Benign
0.11
Sift
Benign
0.15
T;T;T;T
Sift4G
Benign
0.067
T;T;T;T
Polyphen
0.94
P;P;P;P
Vest4
0.61
MutPred
0.41
Gain of methylation at E69 (P = 0.0076);Gain of methylation at E69 (P = 0.0076);Gain of methylation at E69 (P = 0.0076);Gain of methylation at E69 (P = 0.0076);
MVP
0.69
MPC
0.30
ClinPred
0.29
T
GERP RS
3.9
Varity_R
0.45
gMVP
0.50

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: rs1042514343; hg19: chr1-153516336; API