1-153418169-G-T

Variant names:

• chr1-153418169-G-T
• NM_176823.4:c.87G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_176823.4(S100A7A):​c.87G>T​(p.Lys29Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K29E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: S100A7A NM_176823.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.774

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: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]

ACMG classification

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=0.3862944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S100A7A	NM_176823.4	c.87G>T	p.Lys29Asn	missense_variant	Exon 2 of 3	ENST00000368729.9	NP_789793.1
S100A8	NM_001319198.2	c.2+4349C>A		intron_variant	Intron 1 of 2		NP_001306127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
S100A7A	ENST00000368729.9	c.87G>T	p.Lys29Asn	missense_variant	Exon 2 of 3	1	NM_176823.4	ENSP00000357718.3
S100A7A	ENST00000329256.2	c.87G>T	p.Lys29Asn	missense_variant	Exon 1 of 2	1		ENSP00000329008.2
S100A7A	ENST00000368728.2	c.87G>T	p.Lys29Asn	missense_variant	Exon 2 of 3	5		ENSP00000357717.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 29, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.87G>T (p.K29N) alteration is located in exon 2 (coding exon 1) of the S100A7A gene. This alteration results from a G to T substitution at nucleotide position 87, causing the lysine (K) at amino acid position 29 to be replaced by an asparagine (N). 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	Uncertain	0.53
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T;T;T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.43	.;.;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;M;M
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Benign	0.042
Sift	Benign	0.10	T;T;T
Sift4G	Uncertain	0.057	T;T;T
Polyphen		0.99	D;D;D
Vest4		0.40
MutPred		0.57		Loss of ubiquitination at K29 (P = 0.0134);Loss of ubiquitination at K29 (P = 0.0134);Loss of ubiquitination at K29 (P = 0.0134);
MVP		0.25
MPC		0.021
ClinPred		0.58	D
GERP RS		1.5
Varity_R		0.35
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-153390645;