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GeneBe

1-153373945-A-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_005621.2(S100A12):c.161T>A(p.Ile54Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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

4
1
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.98
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 Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.963

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
S100A12NM_005621.2 linkuse as main transcriptc.161T>A p.Ile54Asn missense_variant 3/3 ENST00000368737.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
S100A12ENST00000368737.5 linkuse as main transcriptc.161T>A p.Ile54Asn missense_variant 3/31 NM_005621.2 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
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 GeneticsJan 31, 2022The c.161T>A (p.I54N) alteration is located in exon 3 (coding exon 2) of the S100A12 gene. This alteration results from a T to A substitution at nucleotide position 161, causing the isoleucine (I) at amino acid position 54 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
0.30
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.46
Cadd
Benign
21
Dann
Uncertain
0.98
DEOGEN2
Benign
0.35
T
Eigen
Benign
-0.066
Eigen_PC
Benign
-0.27
FATHMM_MKL
Benign
0.21
N
LIST_S2
Benign
0.58
T
M_CAP
Benign
0.0067
T
MetaRNN
Pathogenic
0.96
D
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.47
T
PROVEAN
Pathogenic
-5.5
D
REVEL
Benign
0.12
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0010
D
Polyphen
0.99
D
Vest4
0.75
MutPred
0.76
Gain of disorder (P = 0.0343);
MVP
0.54
MPC
0.0056
ClinPred
0.96
D
GERP RS
2.5
Varity_R
0.42
gMVP
0.65

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: rs570457059; hg19: chr1-153346421; API