11-18269809-A-C

Variant names:

• chr11-18269809-A-C
• rs1059571
• NM_199161.5:c.323A>C

Variant summary

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

The NM_199161.5(SAA1):​c.323A>C​(p.Lys108Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SAA1 NM_199161.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.77

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]

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=0.31863457).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAA1	NM_199161.5	c.323A>C	p.Lys108Thr	missense_variant	Exon 4 of 4	ENST00000356524.9	NP_954630.2
SAA1	NM_000331.6	c.323A>C	p.Lys108Thr	missense_variant	Exon 4 of 4		NP_000322.3
SAA1	NM_001178006.3	c.323A>C	p.Lys108Thr	missense_variant	Exon 5 of 5		NP_001171477.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAA1	ENST00000356524.9	c.323A>C	p.Lys108Thr	missense_variant	Exon 4 of 4	1	NM_199161.5	ENSP00000348918.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.093	T;T;T
Eigen	Benign	-0.050
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.95	.;.;D
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.1	D;D;D
REVEL	Benign	0.13
Sift	Benign	0.043	D;D;D
Sift4G	Benign	0.30	T;T;T
Vest4		0.21
MutPred		0.49		Loss of ubiquitination at K108 (P = 0.0141);Loss of ubiquitination at K108 (P = 0.0141);Loss of ubiquitination at K108 (P = 0.0141);
MVP		0.095
MPC		0.025
ClinPred		0.91	D
GERP RS		1.2
gMVP		0.50

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: rs1059571; hg19: chr11-18291356;