chr1-153418212-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_176823.4(S100A7A):c.130C>T(p.Leu44Phe) 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 1,461,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

S100A7A
NM_176823.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.850

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3475101).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S100A7A	NM_176823.4 link	c.130C>T	p.Leu44Phe	missense_variant	Exon 2 of 3	ENST00000368729.9	NP_789793.1	Q86SG5
S100A8	NM_001319198.2 link	c.2+4306G>A		intron_variant	Intron 1 of 2		NP_001306127.1	P05109

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
S100A7A	ENST00000368729.9 link	c.130C>T	p.Leu44Phe	missense_variant	Exon 2 of 3	1	NM_176823.4	ENSP00000357718.3	Q86SG5
S100A7A	ENST00000329256.2 link	c.130C>T	p.Leu44Phe	missense_variant	Exon 1 of 2	1		ENSP00000329008.2	Q86SG5
S100A7A	ENST00000368728.2 link	c.130C>T	p.Leu44Phe	missense_variant	Exon 2 of 3	5		ENSP00000357717.1	Q86SG5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251120

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135698

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461698

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.130C>T (p.L44F) alteration is located in exon 2 (coding exon 1) of the S100A7A gene. This alteration results from a C to T substitution at nucleotide position 130, causing the leucine (L) at amino acid position 44 to be replaced by a phenylalanine (F). 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

0.31

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.050

T;T;T

Eigen

Benign

0.033

Eigen_PC

Benign

-0.082

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.77

.;.;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.35

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;M;M

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Benign

0.15

Sift

Benign

0.040

D;D;D

Sift4G

Benign

0.13

T;T;T

Polyphen

0.94

P;P;P

Vest4

0.20

MutPred

0.77

Loss of ubiquitination at K49 (P = 0.0896);Loss of ubiquitination at K49 (P = 0.0896);Loss of ubiquitination at K49 (P = 0.0896);

MVP

0.18

MPC

0.018

ClinPred

0.91

GERP RS

2.4

Varity_R

0.65

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over