rs141189360

Variant summary

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

The NM_020672.3(S100A14):​c.305G>C​(p.Arg102Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R102Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

S100A14
NM_020672.3 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0190
Variant links:
Genes affected
S100A14 (HGNC:18901): (S100 calcium binding protein A14) This gene encodes a member of the S100 protein family which contains an EF-hand motif and binds calcium. The gene is located in a cluster of S100 genes on chromosome 1. Levels of the encoded protein have been found to be lower in cancerous tissue and associated with metastasis suggesting a tumor suppressor function (PMID: 19956863, 19351828). [provided by RefSeq, Dec 2011]

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=0.05537349).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
S100A14NM_020672.3 linkc.305G>C p.Arg102Pro missense_variant Exon 4 of 4 ENST00000344616.4 NP_065723.1 Q9HCY8
S100A14XM_005245362.2 linkc.305G>C p.Arg102Pro missense_variant Exon 4 of 4 XP_005245419.1 Q9HCY8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
S100A14ENST00000344616.4 linkc.305G>C p.Arg102Pro missense_variant Exon 4 of 4 1 NM_020672.3 ENSP00000340463.2 Q9HCY8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461372
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
726982
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.065
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
9.7
DANN
Benign
0.57
DEOGEN2
Benign
0.019
T;T;T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.052
N
LIST_S2
Benign
0.37
.;.;.;T
M_CAP
Benign
0.0050
T
MetaRNN
Benign
0.055
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.69
N;N;N;N
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-1.1
N;N;N;N
REVEL
Benign
0.013
Sift
Benign
0.18
T;T;T;T
Sift4G
Uncertain
0.028
D;D;D;D
Polyphen
0.0
B;B;B;B
Vest4
0.043
MutPred
0.29
Loss of MoRF binding (P = 2e-04);Loss of MoRF binding (P = 2e-04);Loss of MoRF binding (P = 2e-04);Loss of MoRF binding (P = 2e-04);
MVP
0.34
MPC
0.063
ClinPred
0.067
T
GERP RS
-0.68
Varity_R
0.37
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: chr1-153587371; API