11-18269325-A-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_199161.5(SAA1):ā€‹c.222A>Cā€‹(p.Glu74Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0 ( 0 hom., cov: 30)
Exomes š‘“: 0.0000075 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SAA1
NM_199161.5 missense

Scores

4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.82
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 Likely_benign. Variant got -1 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.29223576).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SAA1NM_199161.5 linkuse as main transcriptc.222A>C p.Glu74Asp missense_variant 3/4 ENST00000356524.9
SAA1NM_000331.6 linkuse as main transcriptc.222A>C p.Glu74Asp missense_variant 3/4
SAA1NM_001178006.3 linkuse as main transcriptc.222A>C p.Glu74Asp missense_variant 4/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SAA1ENST00000356524.9 linkuse as main transcriptc.222A>C p.Glu74Asp missense_variant 3/41 NM_199161.5 P1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
151880
Hom.:
0
Cov.:
30
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000746
AC:
10
AN:
1341354
Hom.:
0
Cov.:
39
AF XY:
0.00000916
AC XY:
6
AN XY:
655352
show subpopulations
Gnomad4 AFR exome
AF:
0.0000340
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000442
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000570
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
151880
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
74196
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
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:
0.00
ExAC
AF:
0.000230
AC:
27

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 GeneticsAug 17, 2022The c.222A>C (p.E74D) alteration is located in exon 3 (coding exon 2) of the SAA1 gene. This alteration results from a A to C substitution at nucleotide position 222, causing the glutamic acid (E) at amino acid position 74 to be replaced by an aspartic acid (D). 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
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.13
T;T;.;T
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.51
FATHMM_MKL
Benign
0.52
D
LIST_S2
Uncertain
0.93
.;.;D;D
M_CAP
Benign
0.0036
T
MetaRNN
Benign
0.29
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-2.2
N;N;.;N
REVEL
Benign
0.085
Sift
Uncertain
0.0020
D;D;.;D
Sift4G
Uncertain
0.053
T;T;.;T
Vest4
0.16
MutPred
0.50
Loss of catalytic residue at E74 (P = 0.1685);Loss of catalytic residue at E74 (P = 0.1685);Loss of catalytic residue at E74 (P = 0.1685);Loss of catalytic residue at E74 (P = 0.1685);
MVP
0.18
MPC
2.3
ClinPred
0.051
T
GERP RS
0.74
gMVP
0.42

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

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

Other links and lift over

dbSNP: rs776035778; hg19: chr11-18290872; API