NM_199161.5:c.260T>C

Variant names:

• chr11-18269746-T-C
• rs1059560
• NM_199161.5:c.260T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_199161.5(SAA1):​c.260T>C​(p.Phe87Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000239 in 1,614,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F87L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: SAA1 NM_199161.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.44
• Publications: 0 publications found

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]

ENSG00000303304 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005897194).
• BP6: Variant 11-18269746-T-C is Benign according to our data. Variant chr11-18269746-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 718086.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAA1	NM_199161.5	MANE Select	c.260T>C	p.Phe87Ser	missense	Exon 4 of 4	NP_954630.2	P0DJI8
	SAA1	NM_000331.6		c.260T>C	p.Phe87Ser	missense	Exon 4 of 4	NP_000322.3
	SAA1	NM_001178006.3		c.260T>C	p.Phe87Ser	missense	Exon 5 of 5	NP_001171477.2	P0DJI8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAA1	ENST00000356524.9	TSL:1 MANE Select	c.260T>C	p.Phe87Ser	missense	Exon 4 of 4	ENSP00000348918.4	P0DJI8
	SAA1	ENST00000532858.5	TSL:1	c.260T>C	p.Phe87Ser	missense	Exon 5 of 5	ENSP00000436866.1	P0DJI8
	SAA1	ENST00000405158.2	TSL:5	c.260T>C	p.Phe87Ser	missense	Exon 4 of 4	ENSP00000384906.2	P0DJI8

Frequencies

GnomAD3 genomes AF: 0.00104 AC: 158 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00335

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000850

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: 0.0000294

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000374 AC: 94 AN: 251280 AF XY: 0.000236

Gnomad AFR exome AF: 0.00443

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000155 AC: 227 AN: 1461694 Hom.: 0 Cov.: 31 AF XY: 0.000155 AC XY: 113 AN XY: 727160

African (AFR) AF: 0.00424 AC: 142 AN: 33472

American (AMR) AF: 0.000425 AC: 19 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5762

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1111866

Other (OTH) AF: 0.000563 AC: 34 AN: 60376

GnomAD4 genome AF: 0.00104 AC: 159 AN: 152326 Hom.: 0 Cov.: 33 AF XY: 0.00109 AC XY: 81 AN XY: 74492

African (AFR) AF: 0.00337 AC: 140 AN: 41570

American (AMR) AF: 0.000849 AC: 13 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68022

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.000137 Hom.: 0

ExAC AF: 0.000478 AC: 58

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.12
DANN	Benign	0.34
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.085	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.0059	T
MetaSVM	Benign	-0.97	T
PhyloP100		-1.4
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.39	N
REVEL	Benign	0.014
Sift	Benign	0.54	T
Sift4G	Benign	0.65	T
Vest4		0.083
MVP		0.055
MPC		0.0071
ClinPred		0.0014	T
GERP RS		-3.3
gMVP		0.28
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs1059560; hg19: chr11-18291293;