1-153547804-G-C

Position:

chr1-153547804-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000368713.8(S100A3):c.184C>G(p.Leu62Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00665 in 1,613,956 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0067 ( 42 hom. )

Consequence

S100A3
ENST00000368713.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.10

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:

LOC101928034 (HGNC:):

LOC101928034 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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015061289).

BP6

Variant 1-153547804-G-C is Benign according to our data. Variant chr1-153547804-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3067197.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
S100A3	NM_002960.2 linkuse as main transcript	c.184C>G	p.Leu62Val	missense_variant	3/3	ENST00000368713.8	NP_002951.1
LOC101928034	NR_125947.1 linkuse as main transcript	n.169-617G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
S100A3	ENST00000368713.8 linkuse as main transcript	c.184C>G	p.Leu62Val	missense_variant	3/3	1	NM_002960.2	ENSP00000357702	P1
S100A3	ENST00000368712.1 linkuse as main transcript	c.184C>G	p.Leu62Val	missense_variant	3/3	3		ENSP00000357701	P1
S100A4	ENST00000368714.1 linkuse as main transcript	c.-16+2261C>G		intron_variant		3		ENSP00000357703	P1

Frequencies

GnomAD3 genomes

AF:

0.00586

AC:

891

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000773

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0163

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00856

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00613

AC:

1540

AN:

251392

Hom.:

AF XY:

0.00606

AC XY:

823

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.00388

Gnomad ASJ exome

AF:

0.00278

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000980

Gnomad FIN exome

AF:

0.0160

Gnomad NFE exome

AF:

0.00835

Gnomad OTH exome

AF:

0.00571

GnomAD4 exome

AF:

0.00673

AC:

9841

AN:

1461758

Hom.:

Cov.:

AF XY:

0.00675

AC XY:

4908

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.000956

Gnomad4 AMR exome

AF:

0.00371

Gnomad4 ASJ exome

AF:

0.00257

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00122

Gnomad4 FIN exome

AF:

0.0158

Gnomad4 NFE exome

AF:

0.00740

Gnomad4 OTH exome

AF:

0.00616

GnomAD4 genome

AF:

0.00585

AC:

891

AN:

152198

Hom.:

Cov.:

AF XY:

0.00606

AC XY:

451

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.000771

Gnomad4 AMR

AF:

0.00360

Gnomad4 ASJ

AF:

0.00404

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0163

Gnomad4 NFE

AF:

0.00856

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00777

Hom.:

Bravo

AF:

0.00464

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00733

AC:

ExAC

AF:

0.00636

AC:

772

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00851

EpiControl

AF:

0.00830

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

S100A3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

T;T

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.081

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.77

.;T

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.3

M;M

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.7

D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.027

D;D

Sift4G

Uncertain

0.049

D;D

Polyphen

1.0

D;D

Vest4

0.50

MVP

0.29

MPC

0.20

ClinPred

0.036

GERP RS

1.8

Varity_R

0.48

gMVP

0.40

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