11-18269273-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_199161.5(SAA1):​c.170G>A​(p.Arg57Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000144 in 1,593,572 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R57W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SAA1
NM_199161.5 missense

Scores

1
7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.92
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SAA1NM_199161.5 linkuse as main transcriptc.170G>A p.Arg57Gln missense_variant 3/4 ENST00000356524.9
SAA1NM_000331.6 linkuse as main transcriptc.170G>A p.Arg57Gln missense_variant 3/4
SAA1NM_001178006.3 linkuse as main transcriptc.170G>A p.Arg57Gln missense_variant 4/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SAA1ENST00000356524.9 linkuse as main transcriptc.170G>A p.Arg57Gln missense_variant 3/41 NM_199161.5 P1

Frequencies

GnomAD3 genomes
AF:
0.0000395
AC:
6
AN:
151806
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000727
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000657
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000481
GnomAD3 exomes
AF:
0.0000131
AC:
3
AN:
229470
Hom.:
0
AF XY:
0.00000804
AC XY:
1
AN XY:
124374
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000352
Gnomad FIN exome
AF:
0.0000485
Gnomad NFE exome
AF:
0.00000977
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000118
AC:
17
AN:
1441648
Hom.:
0
Cov.:
49
AF XY:
0.0000112
AC XY:
8
AN XY:
714648
show subpopulations
Gnomad4 AFR exome
AF:
0.0000610
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000237
Gnomad4 FIN exome
AF:
0.0000190
Gnomad4 NFE exome
AF:
0.00000455
Gnomad4 OTH exome
AF:
0.000118
GnomAD4 genome
AF:
0.0000395
AC:
6
AN:
151924
Hom.:
0
Cov.:
30
AF XY:
0.0000269
AC XY:
2
AN XY:
74258
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.0000656
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000476
Bravo
AF:
0.0000756
ExAC
AF:
0.00000826
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 26, 2022The c.170G>A (p.R57Q) alteration is located in exon 3 (coding exon 2) of the SAA1 gene. This alteration results from a G to A substitution at nucleotide position 170, causing the arginine (R) at amino acid position 57 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.069
T
BayesDel_noAF
Benign
-0.23
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.082
T;T;.;T
Eigen
Uncertain
0.49
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.79
.;.;T;D
M_CAP
Benign
0.0047
T
MetaRNN
Uncertain
0.49
T;T;T;T
MetaSVM
Benign
-0.87
T
MutationTaster
Benign
0.92
D;D;D
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-3.5
D;D;.;D
REVEL
Benign
0.21
Sift
Benign
0.087
T;T;.;T
Sift4G
Uncertain
0.037
D;D;.;D
Vest4
0.34
MVP
0.35
MPC
3.1
ClinPred
0.97
D
GERP RS
3.0
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs748089864; hg19: chr11-18290820; API