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GeneBe

1-153374574-G-T

Variant summary

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

The NM_005621.2(S100A12):c.19C>A(p.His7Asn) 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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

S100A12
NM_005621.2 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.29
Variant links:
Genes affected
S100A12 (HGNC:10489): (S100 calcium binding protein A12) 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. This protein is proposed to be involved in specific calcium-dependent signal transduction pathways and its regulatory effect on cytoskeletal components may modulate various neutrophil activities. The protein includes an antimicrobial peptide which has antibacterial activity. [provided by RefSeq, Nov 2014]

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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=0.20823455).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
S100A12NM_005621.2 linkuse as main transcriptc.19C>A p.His7Asn missense_variant 2/3 ENST00000368737.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
S100A12ENST00000368737.5 linkuse as main transcriptc.19C>A p.His7Asn missense_variant 2/31 NM_005621.2 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 GeneticsMar 16, 2022The c.19C>A (p.H7N) alteration is located in exon 2 (coding exon 1) of the S100A12 gene. This alteration results from a C to A substitution at nucleotide position 19, causing the histidine (H) at amino acid position 7 to be replaced by an asparagine (N). 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
0.13
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.79
Cadd
Benign
0.013
Dann
Benign
0.22
DEOGEN2
Benign
0.040
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.019
N
LIST_S2
Benign
0.38
T
M_CAP
Benign
0.0034
T
MetaRNN
Benign
0.21
T
MetaSVM
Benign
-0.93
T
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.85
N
REVEL
Benign
0.012
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.0020
B
Vest4
0.40
MutPred
0.61
Loss of ubiquitination at K3 (P = 0.1223);
MVP
0.18
MPC
0.0050
ClinPred
0.059
T
GERP RS
-2.8
Varity_R
0.13
gMVP
0.36

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: chr1-153347050; API