chr1-153547759-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002960.2(S100A3):c.229C>T(p.Arg77Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000509 in 1,614,030 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00067 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00049 ( 11 hom. )

Consequence

S100A3
NM_002960.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.298

Variant links:

Genes affected

S100A3 (HGNC:10493): (S100 calcium binding protein A3) 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 has the highest content of cysteines of all S100 proteins, has a high affinity for Zinc, and is highly expressed in human hair cuticle. The precise function of this protein is unknown. [provided by RefSeq, Jul 2008]

S100A3 links:

S100A4 (HGNC:10494): (S100 calcium binding protein A4) 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 motility, invasion, and tubulin polymerization. Chromosomal rearrangements and altered expression of this gene have been implicated in tumor metastasis. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

S100A4 links:

LOC101928034 (HGNC:):

LOC101928034 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005070746).

BP6

Variant 1-153547759-G-A is Benign according to our data. Variant chr1-153547759-G-A is described in ClinVar as [Benign]. Clinvar id is 3068065.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S100A3	NM_002960.2 link	c.229C>T	p.Arg77Cys	missense_variant	Exon 3 of 3	ENST00000368713.8	NP_002951.1	P33764
LOC101928034	NR_125947.1 link	n.169-662G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
S100A3	ENST00000368713.8 link	c.229C>T	p.Arg77Cys	missense_variant	Exon 3 of 3	1	NM_002960.2	ENSP00000357702.3	P33764
S100A3	ENST00000368712.1 link	c.229C>T	p.Arg77Cys	missense_variant	Exon 3 of 3	3		ENSP00000357701.1	P33764
S100A4	ENST00000368714.1 link	c.-16+2306C>T		intron_variant	Intron 1 of 2	3		ENSP00000357703.1	P26447

Frequencies

GnomAD3 genomes

AF:

0.000671

AC:

102

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00724

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000998

AC:

251

AN:

251428

AF XY:

0.00130

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000326

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000493

AC:

720

AN:

1461794

Hom.:

Cov.:

AF XY:

0.000683

AC XY:

497

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

AC:

AN:

33480

Gnomad4 AMR exome

AF:

0.0000447

AC:

AN:

44710

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26130

Gnomad4 EAS exome

AF:

0.000504

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.00665

AC:

574

AN:

86258

Gnomad4 FIN exome

AF:

0.0000749

AC:

AN:

53420

Gnomad4 NFE exome

AF:

0.0000369

AC:

AN:

1111942

Gnomad4 Remaining exome

AF:

0.000695

AC:

AN:

60390

Heterozygous variant carriers

120

160

200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000670

AC:

102

AN:

152236

Hom.:

Cov.:

AF XY:

0.000631

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00140

AC:

0.00139645

AN:

0.00139645

Gnomad4 AMR

AF:

0.0000654

AC:

0.0000654108

AN:

0.0000654108

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.000578

AC:

0.000578481

AN:

0.000578481

Gnomad4 SAS

AF:

0.00704

AC:

0.00703934

AN:

0.00703934

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000441

AC:

0.0000441228

AN:

0.0000441228

Gnomad4 OTH

AF:

0.000946

AC:

0.000946074

AN:

0.000946074

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000265

Hom.:

Bravo

AF:

0.000438

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00123

AC:

150

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 04, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0058

T;T

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.81

.;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.0051

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.7

L;L

PrimateAI

Benign

0.29

PROVEAN

Benign

0.79

N;N

REVEL

Benign

0.028

Sift

Benign

0.085

T;T

Sift4G

Benign

0.083

T;T

Polyphen

0.0040

B;B

Vest4

0.088

MVP

0.14

MPC

0.070

ClinPred

0.0086

GERP RS

1.7

Varity_R

0.089

gMVP

0.29

Mutation Taster

=71/29

polymorphism

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.

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