Genetic Variant SAA1:p.Thr5Lys (chr11-18266901-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_199161.5(SAA1):c.14C>A(p.Thr5Lys) 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T5M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Consequence

SAA1
NM_199161.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.112

Publications

1 publications found

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]

SAA1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25359142).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAA1	NM_199161.5	MANE Select	c.14C>A	p.Thr5Lys	missense	Exon 2 of 4	NP_954630.2	P0DJI8
SAA1	NM_000331.6		c.14C>A	p.Thr5Lys	missense	Exon 2 of 4	NP_000322.3
SAA1	NM_001178006.3		c.14C>A	p.Thr5Lys	missense	Exon 3 of 5	NP_001171477.2	P0DJI8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAA1	ENST00000356524.9	TSL:1 MANE Select	c.14C>A	p.Thr5Lys	missense	Exon 2 of 4	ENSP00000348918.4	P0DJI8
SAA1	ENST00000532858.5	TSL:1	c.14C>A	p.Thr5Lys	missense	Exon 3 of 5	ENSP00000436866.1	P0DJI8
SAA1	ENST00000405158.2	TSL:5	c.14C>A	p.Thr5Lys	missense	Exon 2 of 4	ENSP00000384906.2	P0DJI8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.19

Eigen

Benign

-0.090

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.85

M_CAP

Benign

0.0022

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.0

PhyloP100

0.11

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-2.3

REVEL

Benign

0.17

Sift

Uncertain

0.019

Sift4G

Benign

0.069

Vest4

0.60

MutPred

0.41

Gain of ubiquitination at K5 (P = 0.0289)

MVP

0.19

MPC

2.5

ClinPred

0.59

GERP RS

2.8

gMVP

0.71

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over