Genetic Variant S100A1:p.Ala81Gly (chr1-153631798-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006271.2(S100A1):c.242C>G(p.Ala81Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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. A81V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

S100A1
NM_006271.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.55

Publications

0 publications found

Variant links:

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]

S100A1 links:

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]

S100A13 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1705716).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006271.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
S100A1	NM_006271.2	MANE Select	c.242C>G	p.Ala81Gly	missense	Exon 3 of 3	NP_006262.1	A0A0S2Z4H2
S100A13	NM_001024210.2		c.-163+236G>C		intron	N/A	NP_001019381.1	Q99584
S100A13	NM_001437652.1		c.-279+236G>C		intron	N/A	NP_001424581.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
S100A1	ENST00000292169.6	TSL:1 MANE Select	c.242C>G	p.Ala81Gly	missense	Exon 3 of 3	ENSP00000292169.2	P23297
S100A1	ENST00000368696.3	TSL:1	c.*266C>G		3_prime_UTR	Exon 3 of 3	ENSP00000357685.3	Q5T7Y4
S100A1	ENST00000469893.2	TSL:1	n.2380C>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

251150

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.23

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.029

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

PhyloP100

4.6

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.1

REVEL

Benign

0.080

Sift

Benign

0.94

Sift4G

Benign

0.16

Polyphen

0.028

Vest4

0.48

MutPred

0.38

Loss of stability (P = 0.0062)

MVP

0.67

MPC

0.12

ClinPred

0.81

GERP RS

4.2

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.31

gMVP

0.36

Mutation Taster

=52/48

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over