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GeneBe

4-6694043-G-C

Variant summary

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

The NM_005980.3(S100P):c.111G>C(p.Met37Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,910 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: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

S100P
NM_005980.3 missense

Scores

1
1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0200
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]

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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=0.11821225).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
S100PNM_005980.3 linkuse as main transcriptc.111G>C p.Met37Ile missense_variant 1/2 ENST00000296370.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
S100PENST00000296370.4 linkuse as main transcriptc.111G>C p.Met37Ile missense_variant 1/21 NM_005980.3 P1
S100PENST00000513778.1 linkuse as main transcriptn.35+131G>C intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460910
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
726658
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

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 17, 2023The c.111G>C (p.M37I) alteration is located in exon 1 (coding exon 1) of the S100P gene. This alteration results from a G to C substitution at nucleotide position 111, causing the methionine (M) at amino acid position 37 to be replaced by an isoleucine (I). 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
0.63
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
17
DANN
Benign
0.97
DEOGEN2
Benign
0.048
T
Eigen
Benign
-0.58
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.22
N
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.0022
T
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-0.99
T
MutationTaster
Benign
0.96
N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.48
N
REVEL
Benign
0.028
Sift
Benign
0.091
T
Sift4G
Benign
0.16
T
Polyphen
0.0010
B
Vest4
0.11
MutPred
0.55
Loss of disorder (P = 0.0443);
MVP
0.18
MPC
0.071
ClinPred
0.33
T
GERP RS
1.1
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6
Varity_R
0.11
gMVP
0.21

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: rs991472319; hg19: chr4-6695770; API