chr11-18269832-G-T

Variant names:

• chr11-18269832-G-T
• rs1416698471
• NM_199161.5:c.346G>T

Variant summary

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

The NM_199161.5(SAA1):​c.346G>T​(p.Ala116Ser) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SAA1 NM_199161.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.911
• 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: 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=0.047261894).

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.346G>T	p.Ala116Ser	missense	Exon 4 of 4	NP_954630.2	P0DJI8
	SAA1	NM_000331.6		c.346G>T	p.Ala116Ser	missense	Exon 4 of 4	NP_000322.3
	SAA1	NM_001178006.3		c.346G>T	p.Ala116Ser	missense	Exon 5 of 5	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.346G>T	p.Ala116Ser	missense	Exon 4 of 4	ENSP00000348918.4	P0DJI8
	SAA1	ENST00000532858.5	TSL:1	c.346G>T	p.Ala116Ser	missense	Exon 5 of 5	ENSP00000436866.1	P0DJI8
	SAA1	ENST00000405158.2	TSL:5	c.346G>T	p.Ala116Ser	missense	Exon 4 of 4	ENSP00000384906.2	P0DJI8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	1.5
DANN	Benign	0.82
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.98	T
PhyloP100		-0.91
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.087
Sift	Benign	0.57	T
Sift4G	Benign	0.64	T
Vest4		0.10
MutPred		0.31		Gain of glycosylation at A116 (P = 0.0016)
MVP		0.048
MPC		0.0085
ClinPred		0.063	T
GERP RS		-4.1
gMVP		0.12
Mutation Taster		=96/4	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: rs1416698471; hg19: chr11-18291379;