1-153618971-T-C

Variant names:

• chr1-153618971-T-C
• rs200573399
• NM_001024211.2:c.221A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001024211.2(S100A13):​c.221A>G​(p.Asn74Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,613,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000047 (0 hom.)
• Consequence: S100A13 NM_001024211.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.104

Genes affected

S100A13 (HGNC:10490): (S100 calcium binding protein A13) 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 is widely expressed in various types of tissues with a high expression level in thyroid gland. In smooth muscle cells, this protein co-expresses with other family members in the nucleus and in stress fibers, suggesting diverse functions in signal transduction. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.025251925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S100A13	NM_001024211.2	c.221A>G	p.Asn74Ser	missense_variant	Exon 3 of 3	ENST00000476133.6	NP_001019382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
S100A13	ENST00000476133.6	c.221A>G	p.Asn74Ser	missense_variant	Exon 3 of 3	1	NM_001024211.2	ENSP00000507299.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152108 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000954 AC: 24 AN: 251486 AF XY: 0.0000441

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000465 AC: 68 AN: 1461350 Hom.: 0 Cov.: 30 AF XY: 0.0000385 AC XY: 28 AN XY: 727012

Gnomad4 AFR exome AF: 0.000149 AC: 5 AN: 33474

Gnomad4 AMR exome AF: 0.000201 AC: 9 AN: 44722

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26132

Gnomad4 EAS exome AF: 0.000101 AC: 4 AN: 39696

Gnomad4 SAS exome AF: 0.000186 AC: 16 AN: 86248

Gnomad4 FIN exome AF: 0.0000187 AC: 1 AN: 53382

Gnomad4 NFE exome AF: 0.0000252 AC: 28 AN: 1111548

Gnomad4 Remaining exome AF: 0.0000828 AC: 5 AN: 60382

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152226 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74424

Gnomad4 AFR AF: 0.0000241 AC: 0.0000240662 AN: 0.0000240662

Gnomad4 AMR AF: 0.000131 AC: 0.00013089 AN: 0.00013089

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000207 AC: 0.000207211 AN: 0.000207211

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.00 AC: 0 AN: 0

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000680

ExAC AF: 0.0000659 AC: 8

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.221A>G (p.N74S) alteration is located in exon 5 (coding exon 2) of the S100A13 gene. This alteration results from a A to G substitution at nucleotide position 221, causing the asparagine (N) at amino acid position 74 to be replaced by a serine (S). 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	0.060
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.8
DANN	Benign	0.82
DEOGEN2	Benign	0.0076	T;T;T;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.71	.;.;T;.
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.025	T;T;T;T
MetaSVM	Benign	-0.92	T
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.49	N;N;N;N
REVEL	Benign	0.031
Sift	Benign	0.74	T;T;T;T
Sift4G	Benign	0.74	T;T;T;T
Polyphen		0.0	B;B;B;B
Vest4		0.11
MVP		0.13
ClinPred		0.010	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.097
gMVP		0.20
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs200573399; hg19: chr1-153591447;