11-18269817-AAT-TCG

Variant names:

• chr11-18269817-AAT-TCG
• NM_199161.5:c.331_333delAATinsTCG
• SAA1 p.Asn111Ser

Variant summary

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

The NM_199161.5(SAA1):​c.331_333delAATinsTCG​(p.Asn111Ser) variant causes a missense change. 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: 33)
• Consequence: SAA1 NM_199161.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.39
• Publications: 0 publications found

Genes affected

SAA1 (HGNC:10513): (serum amyloid A1) This gene encodes a member of the serum amyloid A family of apolipoproteins. The encoded preproprotein is proteolytically processed to generate the mature protein. This protein is a major acute phase protein that is highly expressed in response to inflammation and tissue injury. This protein also plays an important role in HDL metabolism and cholesterol homeostasis. High levels of this protein are associated with chronic inflammatory diseases including atherosclerosis, rheumatoid arthritis, Alzheimer's disease and Crohn's disease. This protein may also be a potential biomarker for certain tumors. Finally, antimicrobial activity against S. aureus and E. coli resides in the N-terminal portion of the mature protein. Alternate splicing results in multiple transcript variants that encode the same protein. A pseudogene of this gene is found on chromosome 11. [provided by RefSeq, Jul 2020]

ENSG00000303304 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199161.5. 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
	SAA1	NM_199161.5	MANE Select	c.331_333delAATinsTCG	p.Asn111Ser	missense	N/A	NP_954630.2	P0DJI8
	SAA1	NM_000331.6		c.331_333delAATinsTCG	p.Asn111Ser	missense	N/A	NP_000322.3
	SAA1	NM_001178006.3		c.331_333delAATinsTCG	p.Asn111Ser	missense	N/A	NP_001171477.2	P0DJI8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAA1	ENST00000356524.9	TSL:1 MANE Select	c.331_333delAATinsTCG	p.Asn111Ser	missense	N/A	ENSP00000348918.4	P0DJI8
	SAA1	ENST00000532858.5	TSL:1	c.331_333delAATinsTCG	p.Asn111Ser	missense	N/A	ENSP00000436866.1	P0DJI8
	SAA1	ENST00000405158.2	TSL:5	c.331_333delAATinsTCG	p.Asn111Ser	missense	N/A	ENSP00000384906.2	P0DJI8

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.4

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: chr11-18291364;