1-153390416-GGT-CGC

Variant names:

• chr1-153390416-GGT-CGC
• NM_002964.5:c.118_120delACCinsGCG
• S100A8 p.Thr40Ala

Variant summary

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

The NM_002964.5(S100A8):​c.118_120delACCinsGCG​(p.Thr40Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: S100A8 NM_002964.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256
• Publications: 0 publications found

Genes affected

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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002964.5. 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
	S100A8	NM_002964.5	MANE Select	c.118_120delACCinsGCG	p.Thr40Ala	missense	N/A	NP_002955.2
	S100A8	NM_001319196.1		c.190_192delACCinsGCG	p.Thr64Ala	missense	N/A	NP_001306125.1
	S100A8	NM_001319197.1		c.187_189delACCinsGCG	p.Thr63Ala	missense	N/A	NP_001306126.1	P05109

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100A8	ENST00000368733.4	TSL:1 MANE Select	c.118_120delACCinsGCG	p.Thr40Ala	missense	N/A	ENSP00000357722.3	P05109
	S100A8	ENST00000477801.1	TSL:1	n.654_656delACCinsGCG		non_coding_transcript_exon	Exon 1 of 2
	S100A8	ENST00000368732.5	TSL:3	c.118_120delACCinsGCG	p.Thr40Ala	missense	N/A	ENSP00000357721.1	P05109

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.26

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-153362892;