NM_199161.5:c.224T>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_199161.5(SAA1):c.224T>C(p.Val75Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 147,752 control chromosomes in the GnomAD database, including 23,233 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 23233 hom., cov: 28)

Exomes 𝑓: 0.60 ( 180767 hom. )

Failed GnomAD Quality Control

Consequence

SAA1
NM_199161.5 missense

Scores

Splicing: ADA: 0.00008927

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.68

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050112307).

BP6

Variant 11-18269327-T-C is Benign according to our data. Variant chr11-18269327-T-C is described in ClinVar as [Benign]. Clinvar id is 1258441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAA1	NM_199161.5 link	c.224T>C	p.Val75Ala	missense_variant	Exon 3 of 4	ENST00000356524.9	NP_954630.2	P0DJI8
SAA1	NM_000331.6 link	c.224T>C	p.Val75Ala	missense_variant	Exon 3 of 4		NP_000322.3	P0DJI8
SAA1	NM_001178006.3 link	c.224T>C	p.Val75Ala	missense_variant	Exon 4 of 5		NP_001171477.2	P0DJI8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAA1	ENST00000356524.9 link	c.224T>C	p.Val75Ala	missense_variant	Exon 3 of 4	1	NM_199161.5	ENSP00000348918.4		P0DJI8

Frequencies

GnomAD3 genomes

AF:

0.601

AC:

88766

AN:

147632

Hom.:

23206

Cov.:

show subpopulations

Gnomad AFR

AF:

0.568

Gnomad AMI

AF:

0.474

Gnomad AMR

AF:

0.542

Gnomad ASJ

AF:

0.461

Gnomad EAS

AF:

0.557

Gnomad SAS

AF:

0.576

Gnomad FIN

AF:

0.703

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.636

Gnomad OTH

AF:

0.557

GnomAD3 exomes

AF:

0.534

AC:

63227

AN:

118470

Hom.:

11715

AF XY:

0.532

AC XY:

32497

AN XY:

61134

show subpopulations

Gnomad AFR exome

AF:

0.517

Gnomad AMR exome

AF:

0.474

Gnomad ASJ exome

AF:

0.405

Gnomad EAS exome

AF:

0.486

Gnomad SAS exome

AF:

0.500

Gnomad FIN exome

AF:

0.611

Gnomad NFE exome

AF:

0.559

Gnomad OTH exome

AF:

0.530

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.601

AC:

781752

AN:

1300906

Hom.:

180767

Cov.:

AF XY:

0.598

AC XY:

379637

AN XY:

635044

show subpopulations

Gnomad4 AFR exome

AF:

0.535

Gnomad4 AMR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.428

Gnomad4 EAS exome

AF:

0.533

Gnomad4 SAS exome

AF:

0.532

Gnomad4 FIN exome

AF:

0.682

Gnomad4 NFE exome

AF:

0.614

Gnomad4 OTH exome

AF:

0.576

GnomAD4 genome

AF:

0.601

AC:

88846

AN:

147752

Hom.:

23233

Cov.:

AF XY:

0.601

AC XY:

43410

AN XY:

72224

show subpopulations

Gnomad4 AFR

AF:

0.568

Gnomad4 AMR

AF:

0.542

Gnomad4 ASJ

AF:

0.461

Gnomad4 EAS

AF:

0.557

Gnomad4 SAS

AF:

0.576

Gnomad4 FIN

AF:

0.703

Gnomad4 NFE

AF:

0.636

Gnomad4 OTH

AF:

0.557

Alfa

AF:

0.634

Hom.:

3289

ExAC

AF:

0.551

AC:

63027

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 30, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 23437051) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.079

T;T;.;T

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.39

.;.;T;T

MetaRNN

Benign

0.0050

T;T;T;T

MetaSVM

Benign

-0.89

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-3.5

D;D;.;D

REVEL

Benign

0.17

Sift

Benign

0.034

D;D;.;D

Sift4G

Uncertain

0.019

D;D;.;D

Vest4

0.077

MPC

2.5

ClinPred

0.060

GERP RS

-3.1

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000089

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over