1-153419293-C-A

Position:

• chr1-153419293-C-A

Variant summary

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

The NM_176823.4(S100A7A):​c.290C>A​(p.Ser97Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: S100A7A NM_176823.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.202

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]

S100A8 (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=0.14967448).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
S100A7A	NM_176823.4	c.290C>A	p.Ser97Tyr	missense_variant	3/3	ENST00000368729.9
S100A8	NM_001319198.2	c.2+3225G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
S100A7A	ENST00000368729.9	c.290C>A	p.Ser97Tyr	missense_variant	3/3	1	NM_176823.4	P1
S100A7A	ENST00000329256.2	c.290C>A	p.Ser97Tyr	missense_variant	2/2	1		P1
S100A7A	ENST00000368728.2	c.290C>A	p.Ser97Tyr	missense_variant	3/3	5		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

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

Jan 31, 2022

The c.290C>A (p.S97Y) alteration is located in exon 3 (coding exon 2) of the S100A7A gene. This alteration results from a C to A substitution at nucleotide position 290, causing the serine (S) at amino acid position 97 to be replaced by a tyrosine (Y). 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	0.14
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.1
DANN	Benign	0.77
DEOGEN2	Benign	0.048	T;T;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.012	N
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.4	M;M;M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.057
Sift	Uncertain	0.025	D;D;D
Sift4G	Benign	0.23	T;T;T
Polyphen		0.92	P;P;P
Vest4		0.16
MutPred		0.41		Loss of glycosylation at S97 (P = 0.0218);Loss of glycosylation at S97 (P = 0.0218);Loss of glycosylation at S97 (P = 0.0218);
MVP		0.16
MPC		0.013
ClinPred		0.22	T
GERP RS		0.77
Varity_R		0.062
gMVP		0.091

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: rs1337429087; hg19: chr1-153391769;