Genetic Variant NM_176823.4:c.53A>G (chr1-153418135-A-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1PM2

The NM_176823.4(S100A7A):c.53A>G(p.His18Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/22 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. H18L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

S100A7A
NM_176823.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.31

Publications

0 publications found

Variant links:

Genes affected

S100A7A (HGNC:21657): (S100 calcium binding protein A7A) Enables protein self-association. Predicted to act upstream of or within inflammatory response. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

S100A7A links:

S100A8 (HGNC:10498): (S100 calcium binding protein A8) 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 the inhibition of casein kinase and as a cytokine. Altered expression of this protein is associated with the disease cystic fibrosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

S100A8 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity S1A7A_HUMAN

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176823.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100A7A	NM_176823.4	MANE Select	c.53A>G	p.His18Arg	missense	Exon 2 of 3	NP_789793.1	Q86SG5
	S100A8	NM_001319198.2		c.2+4383T>C		intron	N/A	NP_001306127.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
S100A7A	ENST00000368729.9	TSL:1 MANE Select	c.53A>G	p.His18Arg	missense	Exon 2 of 3	ENSP00000357718.3	Q86SG5
S100A7A	ENST00000329256.2	TSL:1	c.53A>G	p.His18Arg	missense	Exon 1 of 2	ENSP00000329008.2	Q86SG5
S100A7A	ENST00000368728.2	TSL:5	c.53A>G	p.His18Arg	missense	Exon 2 of 3	ENSP00000357717.1	Q86SG5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.085

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.37

M_CAP

Benign

0.00097

MetaRNN

Uncertain

0.66

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PhyloP100

1.3

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-6.2

REVEL

Benign

0.10

Sift

Benign

0.078

Sift4G

Benign

0.17

Polyphen

0.98

Vest4

0.38

MutPred

0.78

Gain of MoRF binding (P = 0.0122)

MVP

0.18

MPC

0.019

ClinPred

0.33

GERP RS

1.2

PromoterAI

0.088

Neutral

(source)

Varity_R

0.61

gMVP

0.31

Mutation Taster

=80/20

polymorphism

(source)

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

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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