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GeneBe

4-6696945-A-G

Variant summary

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

The NM_005980.3(S100P):c.191A>G(p.Asn64Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000151 in 1,461,426 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 35)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

S100P
NM_005980.3 missense

Scores

1
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.51
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 Uncertain_significance. Variant got 4 ACMG points.

PM1
In a mutagenesis_site In S100Ppa; permanently active, interacts with EZR and PPP5C in absence of calcium; when associated with 21-S--G-23, K-68 and S-73. (size 0) in uniprot entity S100P_HUMAN
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
S100PNM_005980.3 linkuse as main transcriptc.191A>G p.Asn64Ser missense_variant 2/2 ENST00000296370.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
S100PENST00000296370.4 linkuse as main transcriptc.191A>G p.Asn64Ser missense_variant 2/21 NM_005980.3 P1
S100PENST00000513778.1 linkuse as main transcriptn.88A>G non_coding_transcript_exon_variant 2/23

Frequencies

GnomAD3 genomes
Cov.:
35
GnomAD4 exome
AF:
0.0000151
AC:
22
AN:
1461426
Hom.:
0
Cov.:
31
AF XY:
0.0000165
AC XY:
12
AN XY:
727026
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
35

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 GeneticsMay 23, 2023The c.191A>G (p.N64S) alteration is located in exon 2 (coding exon 2) of the S100P gene. This alteration results from a A to G substitution at nucleotide position 191, causing the asparagine (N) at amino acid position 64 to be replaced by a serine (S). 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
0.20
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.46
T
Eigen
Benign
0.11
Eigen_PC
Benign
-0.014
FATHMM_MKL
Benign
0.74
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.0062
T
MetaRNN
Uncertain
0.51
D
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.36
T
PROVEAN
Pathogenic
-4.4
D
REVEL
Benign
0.17
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.014
D
Polyphen
0.97
D
Vest4
0.23
MutPred
0.70
Gain of disorder (P = 0.0554);
MVP
0.38
MPC
0.34
ClinPred
0.94
D
GERP RS
3.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.34
gMVP
0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-6698672; API