1-153419158-T-A

Variant names:

• chr1-153419158-T-A
• rs775484804
• NM_176823.4:c.155T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_176823.4(S100A7A):​c.155T>A​(p.Ile52Lys) 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. 16/22 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. I52T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: S100A7A NM_176823.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.72
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034570158).

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.155T>A	p.Ile52Lys	missense	Exon 3 of 3	NP_789793.1	Q86SG5
	S100A8	NM_001319198.2		c.2+3360A>T		intron	N/A	NP_001306127.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100A7A	ENST00000368729.9	TSL:1 MANE Select	c.155T>A	p.Ile52Lys	missense	Exon 3 of 3	ENSP00000357718.3	Q86SG5
	S100A7A	ENST00000329256.2	TSL:1	c.155T>A	p.Ile52Lys	missense	Exon 2 of 2	ENSP00000329008.2	Q86SG5
	S100A7A	ENST00000368728.2	TSL:5	c.155T>A	p.Ile52Lys	missense	Exon 3 of 3	ENSP00000357717.1	Q86SG5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.0010
DANN	Benign	0.22
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-1.1	N
PhyloP100		-2.7
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.84	N
REVEL	Benign	0.019
Sift	Benign	0.99	T
Sift4G	Benign	0.25	T
Polyphen		0.0	B
Vest4		0.068
MutPred		0.43		Gain of disorder (P = 0.0019)
MVP		0.061
MPC		0.0041
ClinPred		0.053	T
GERP RS		-3.4
Varity_R		0.063
gMVP		0.15
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs775484804; hg19: chr1-153391634;