Variant chr21-46599370-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_006272.3(S100B):c.272A>G(p.His91Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,500 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

S100B
NM_006272.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

Variant links:

Genes affected

S100B (HGNC:10500): (S100 calcium binding protein B) 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 21q22.3. This protein may function in Neurite extension, proliferation of melanoma cells, stimulation of Ca2+ fluxes, inhibition of PKC-mediated phosphorylation, astrocytosis and axonal proliferation, and inhibition of microtubule assembly. Chromosomal rearrangements and altered expression of this gene have been implicated in several neurological, neoplastic, and other types of diseases, including Alzheimer's disease, Down's syndrome, epilepsy, amyotrophic lateral sclerosis, melanoma, and type I diabetes. [provided by RefSeq, Jul 2008]

S100B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity S100B_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.090230465).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
S100B	NM_006272.3 linkuse as main transcript	c.272A>G	p.His91Arg	missense_variant	3/3	ENST00000291700.9	NP_006263.1
S100B	XM_017028424.3 linkuse as main transcript	c.272A>G	p.His91Arg	missense_variant	3/3		XP_016883913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
S100B	ENST00000291700.9 linkuse as main transcript	c.272A>G	p.His91Arg	missense_variant	3/3	1	NM_006272.3	ENSP00000291700	P1
S100B	ENST00000397648.1 linkuse as main transcript	c.272A>G	p.His91Arg	missense_variant	2/2	1		ENSP00000380769	P1
S100B	ENST00000367071.4 linkuse as main transcript	c.*81A>G		3_prime_UTR_variant	4/4	1		ENSP00000356038

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

250998

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135636

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000203

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:

0.00000479

AC:

AN:

1461500

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

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

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

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 submitter

clinical testing

Ambry Genetics

Dec 16, 2022

The c.272A>G (p.H91R) alteration is located in exon 3 (coding exon 2) of the S100B gene. This alteration results from a A to G substitution at nucleotide position 272, causing the histidine (H) at amino acid position 91 to be replaced by an arginine (R). 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

0.066

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.060

T;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.099

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.79

.;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.090

T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.38

N;N

REVEL

Benign

0.041

Sift

Benign

0.18

T;T

Sift4G

Benign

0.32

T;T

Polyphen

0.047

B;B

Vest4

0.23

MutPred

0.28

Gain of solvent accessibility (P = 0.0971);Gain of solvent accessibility (P = 0.0971);

MVP

0.40

MPC

0.35

ClinPred

0.033

GERP RS

4.0

Varity_R

0.38

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over