Menu
GeneBe

1-153390418-T-C

Variant summary

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

The NM_002964.5(S100A8):c.118A>G(p.Thr40Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

S100A8
NM_002964.5 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.256
Variant links:
Genes affected
S100A8 (HGNC:10498): (S100 calcium binding protein A8) 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 may function in the inhibition of casein kinase and as a cytokine. Altered expression of this protein is associated with the disease cystic fibrosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

Genome browser will be placed here

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=0.10910708).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
S100A8NM_002964.5 linkuse as main transcriptc.118A>G p.Thr40Ala missense_variant 2/3 ENST00000368733.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
S100A8ENST00000368733.4 linkuse as main transcriptc.118A>G p.Thr40Ala missense_variant 2/31 NM_002964.5 P1
S100A8ENST00000477801.1 linkuse as main transcriptn.654A>G non_coding_transcript_exon_variant 1/21
S100A8ENST00000368732.5 linkuse as main transcriptc.118A>G p.Thr40Ala missense_variant 2/33 P1

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152028
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000386
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251476
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135910
show subpopulations
Gnomad AFR exome
AF:
0.000246
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461892
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727248
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152028
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74252
show subpopulations
Gnomad4 AFR
AF:
0.000386
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000756
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000412
AC:
5

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 GeneticsDec 20, 2023The c.118A>G (p.T40A) alteration is located in exon 2 (coding exon 1) of the S100A8 gene. This alteration results from a A to G substitution at nucleotide position 118, causing the threonine (T) at amino acid position 40 to be replaced by an alanine (A). 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
0.085
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-0.68
Cadd
Benign
4.3
Dann
Benign
0.92
DEOGEN2
Benign
0.21
T;T
Eigen
Benign
-0.71
Eigen_PC
Benign
-0.87
FATHMM_MKL
Benign
0.039
N
M_CAP
Benign
0.0039
T
MetaRNN
Benign
0.11
T;T
MetaSVM
Benign
-0.94
T
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-2.1
N;N
REVEL
Benign
0.029
Sift
Benign
0.054
T;T
Sift4G
Benign
0.53
T;T
Polyphen
0.63
P;P
Vest4
0.18
MVP
0.25
MPC
0.24
ClinPred
0.052
T
GERP RS
-1.1
Varity_R
0.25
gMVP
0.13

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs139987242; hg19: chr1-153362894; API