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GeneBe

4-6697022-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005980.3(S100P):c.268G>C(p.Glu90Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,613,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

S100P
NM_005980.3 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.179
Variant links:
Genes affected
S100P (HGNC:10504): (S100 calcium binding protein P) 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; however, this gene is located at 4p16. This protein, in addition to binding Ca2+, also binds Zn2+ and Mg2+. This protein may play a role in the etiology of prostate cancer. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.019124746).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
S100PNM_005980.3 linkuse as main transcriptc.268G>C p.Glu90Gln missense_variant 2/2 ENST00000296370.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
S100PENST00000296370.4 linkuse as main transcriptc.268G>C p.Glu90Gln missense_variant 2/21 NM_005980.3 P1
S100PENST00000513778.1 linkuse as main transcriptn.165G>C non_coding_transcript_exon_variant 2/23

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152246
Hom.:
0
Cov.:
33
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:
0.000827
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
250770
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135538
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:
0.000197
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000205
AC:
30
AN:
1461118
Hom.:
0
Cov.:
31
AF XY:
0.0000220
AC XY:
16
AN XY:
726878
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:
0.000302
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152246
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74390
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:
0.000827
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.0000247
AC:
3

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 GeneticsAug 14, 2023The c.268G>C (p.E90Q) alteration is located in exon 2 (coding exon 2) of the S100P gene. This alteration results from a G to C substitution at nucleotide position 268, causing the glutamic acid (E) at amino acid position 90 to be replaced by a glutamine (Q). 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
0.069
BayesDel_addAF
Benign
-0.62
T
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.89
DANN
Benign
0.049
DEOGEN2
Benign
0.027
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.020
N
LIST_S2
Benign
0.42
T
M_CAP
Benign
0.00073
T
MetaRNN
Benign
0.019
T
MetaSVM
Benign
-0.94
T
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.32
N
REVEL
Benign
0.010
Sift
Benign
1.0
T
Sift4G
Benign
0.67
T
Polyphen
0.0
B
Vest4
0.049
MutPred
0.30
Gain of MoRF binding (P = 0.0145);
MVP
0.26
MPC
0.064
ClinPred
0.011
T
GERP RS
-6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.24
gMVP
0.070

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: rs775589745; hg19: chr4-6698749; API