rs367888712

Variant names:

• chr1-153630640-C-A
• rs367888712
• NM_006271.2:c.119C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-153630640-C-A
• chr1-153630640-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006271.2(S100A1):​c.119C>A​(p.Thr40Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T40M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: S100A1 NM_006271.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.680

Genes affected

S100A1 (HGNC:10486): (S100 calcium binding protein A1) 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 stimulation of Ca2+-induced Ca2+ release, inhibition of microtubule assembly, and inhibition of protein kinase C-mediated phosphorylation. Reduced expression of this protein has been implicated in cardiomyopathies. [provided by RefSeq, Jul 2008]

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]

ENSG00000271853 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0941942).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S100A1	NM_006271.2	c.119C>A	p.Thr40Lys	missense_variant	Exon 2 of 3	ENST00000292169.6	NP_006262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
S100A1	ENST00000292169.6	c.119C>A	p.Thr40Lys	missense_variant	Exon 2 of 3	1	NM_006271.2	ENSP00000292169.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461816 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727220

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.89
DEOGEN2	Benign	0.00082	T;T;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.094	T;T;T
MetaSVM	Benign	-0.94	T
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.91	N;N;N
REVEL	Benign	0.058
Sift	Benign	0.70	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.14	.;B;.
Vest4		0.30
MutPred		0.34		.;Gain of ubiquitination at T40 (P = 0.0162);Gain of ubiquitination at T40 (P = 0.0162);
MVP		0.37
MPC		0.13
ClinPred		0.21	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.59

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: rs367888712; hg19: chr1-153603116;