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GeneBe

4-6696929-A-G

Variant summary

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

The NM_005980.3(S100P):c.175A>G(p.Lys59Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 35)

Consequence

S100P
NM_005980.3 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.775
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=0.10433018).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
S100PNM_005980.3 linkuse as main transcriptc.175A>G p.Lys59Glu missense_variant 2/2 ENST00000296370.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
S100PENST00000296370.4 linkuse as main transcriptc.175A>G p.Lys59Glu missense_variant 2/21 NM_005980.3 P1
S100PENST00000513778.1 linkuse as main transcriptn.72A>G non_coding_transcript_exon_variant 2/23

Frequencies

GnomAD3 genomes
Cov.:
35
GnomAD4 exome
Cov.:
31
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 11, 2022The c.175A>G (p.K59E) 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 175, causing the lysine (K) at amino acid position 59 to be replaced by a glutamic acid (E). 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
0.32
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
16
DANN
Uncertain
1.0
DEOGEN2
Benign
0.082
T
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.30
FATHMM_MKL
Benign
0.67
D
LIST_S2
Benign
0.65
T
M_CAP
Benign
0.0029
T
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-0.98
T
MutationTaster
Benign
0.86
N
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.017
Sift
Benign
0.061
T
Sift4G
Uncertain
0.042
D
Polyphen
0.12
B
Vest4
0.097
MutPred
0.41
Loss of ubiquitination at K59 (P = 0.0174);
MVP
0.40
MPC
0.13
ClinPred
0.95
D
GERP RS
2.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.37
gMVP
0.25

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: chr4-6698656; API