11-18269302-C-T

Variant summary

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

The NM_199161.5(SAA1):​c.199C>T​(p.Pro67Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SAA1
NM_199161.5 missense

Scores

1
3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.06
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.199C>T p.Pro67Ser missense_variant 3/4 ENST00000356524.9
SAA1NM_000331.6 linkuse as main transcriptc.199C>T p.Pro67Ser missense_variant 3/4
SAA1NM_001178006.3 linkuse as main transcriptc.199C>T p.Pro67Ser missense_variant 4/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SAA1ENST00000356524.9 linkuse as main transcriptc.199C>T p.Pro67Ser missense_variant 3/41 NM_199161.5 P1

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000143
AC:
2
AN:
1396928
Hom.:
0
Cov.:
48
AF XY:
0.00000145
AC XY:
1
AN XY:
688236
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000185
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30

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 GeneticsSep 12, 2023The c.199C>T (p.P67S) alteration is located in exon 3 (coding exon 2) of the SAA1 gene. This alteration results from a C to T substitution at nucleotide position 199, causing the proline (P) at amino acid position 67 to be replaced by a serine (S). 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
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.092
T;T;.;T
Eigen
Uncertain
0.21
Eigen_PC
Benign
-0.0082
FATHMM_MKL
Benign
0.43
N
LIST_S2
Benign
0.84
.;.;T;D
M_CAP
Benign
0.0045
T
MetaRNN
Uncertain
0.57
D;D;D;D
MetaSVM
Benign
-0.79
T
MutationTaster
Benign
0.57
D;D;D
PrimateAI
Benign
0.42
T
PROVEAN
Pathogenic
-6.6
D;D;.;D
REVEL
Benign
0.16
Sift
Benign
0.15
T;T;.;T
Sift4G
Benign
0.080
T;T;.;T
Vest4
0.23
MutPred
0.69
Gain of glycosylation at P67 (P = 0.0266);Gain of glycosylation at P67 (P = 0.0266);Gain of glycosylation at P67 (P = 0.0266);Gain of glycosylation at P67 (P = 0.0266);
MVP
0.55
MPC
3.0
ClinPred
0.99
D
GERP RS
3.2
gMVP
0.44

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-18290849; API