1-153626453-G-A

Position:

• chr1-153626453-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The ENST00000476133.6(S100A13):​c.20C>T​(p.Thr7Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: S100A13 ENST00000476133.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.95

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.811

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
S100A13	NM_001024211.2	c.20C>T	p.Thr7Ile	missense_variant	2/3	ENST00000476133.6	NP_001019382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
S100A13	ENST00000476133.6	c.20C>T	p.Thr7Ile	missense_variant	2/3	1	NM_001024211.2	ENSP00000507299	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 12, 2021

The c.20C>T (p.T7I) alteration is located in exon 4 (coding exon 1) of the S100A13 gene. This alteration results from a C to T substitution at nucleotide position 20, causing the threonine (T) at amino acid position 7 to be replaced by an isoleucine (I). 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	Pathogenic	0.88
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T;T;T;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.76	.;.;T;.
M_CAP	Benign	0.053	D
MetaRNN	Pathogenic	0.81	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.93	D;D;D;D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.9	D;D;D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0030	D;D;D;D
Sift4G	Uncertain	0.020	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.84
MutPred		0.49		Loss of disorder (P = 0.0358);Loss of disorder (P = 0.0358);Loss of disorder (P = 0.0358);Loss of disorder (P = 0.0358);
MVP		0.40
ClinPred		0.97	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.46
gMVP		0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-153598929;