1-153547804-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002960.2(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 NM_002960.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.10

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]

LOC101928034 (HGNC:):

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]

ACMG classification

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 GnomAd at 6 AR gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00586 AC: 891 AN: 152080 Hom.: 6 Cov.: 32

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.: 5 AF XY: 0.00606 AC XY: 823 AN XY: 135864

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.: 42 Cov.: 31 AF XY: 0.00675 AC XY: 4908 AN XY: 727204

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.: 6 Cov.: 32 AF XY: 0.00606 AC XY: 451 AN XY: 74402

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.: 6

Bravo AF: 0.00464

TwinsUK AF: 0.00863 AC: 32

ALSPAC AF: 0.00649 AC: 25

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00733 AC: 63

ExAC AF: 0.00636 AC: 772

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00851

EpiControl AF: 0.00830

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.34
Cadd	Benign	20
Dann	Uncertain	0.99
DEOGEN2	Benign	0.33	T;T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.081
FATHMM_MKL	Benign	0.72	D
MetaRNN	Benign	0.015	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.3	M;M
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Benign	0.48	T
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	T
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

Other links and lift over

dbSNP: rs116208483; hg19: chr1-153520280; COSMIC: COSV105279822; COSMIC: COSV105279822;