NM_199161.5:c.256T>C

Variant names:

• chr11-18269742-T-C
• rs1059559
• NM_199161.5:c.256T>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.256T>C​(p.Phe86Leu) 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 1,614,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: SAA1 NM_199161.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.88
• Publications: 6 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=0.0037888587).
• BP6: Variant 11-18269742-T-C is Benign according to our data. Variant chr11-18269742-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 717982.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.256T>C	p.Phe86Leu	missense	Exon 4 of 4	NP_954630.2
	SAA1	NM_000331.6		c.256T>C	p.Phe86Leu	missense	Exon 4 of 4	NP_000322.3
	SAA1	NM_001178006.3		c.256T>C	p.Phe86Leu	missense	Exon 5 of 5	NP_001171477.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAA1	ENST00000356524.9	TSL:1 MANE Select	c.256T>C	p.Phe86Leu	missense	Exon 4 of 4	ENSP00000348918.4
	SAA1	ENST00000532858.5	TSL:1	c.256T>C	p.Phe86Leu	missense	Exon 5 of 5	ENSP00000436866.1
	SAA1	ENST00000405158.2	TSL:5	c.256T>C	p.Phe86Leu	missense	Exon 4 of 4	ENSP00000384906.2

Frequencies

GnomAD3 genomes AF: 0.00104 AC: 159 AN: 152204 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00338

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: 0.000386 AC: 97 AN: 251264 AF XY: 0.000258

Gnomad AFR exome AF: 0.00449

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000155 AC: 226 AN: 1461686 Hom.: 0 Cov.: 31 AF XY: 0.000157 AC XY: 114 AN XY: 727160

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

American (AMR) AF: 0.000425 AC: 19 AN: 44712

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

East Asian (EAS) AF: 0.0000252 AC: 1 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: 0.0000189 AC: 21 AN: 1111860

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

GnomAD4 genome AF: 0.00105 AC: 160 AN: 152322 Hom.: 0 Cov.: 33 AF XY: 0.00109 AC XY: 81 AN XY: 74492

African (AFR) AF: 0.00339 AC: 141 AN: 41566

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68028

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.000142 Hom.: 0

ExAC AF: 0.000494 AC: 60

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	Uncertain	0.41
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.0010
DANN	Benign	0.21
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.5
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.070	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-0.95	T
PhyloP100		-4.9
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.022
Sift	Benign	0.85	T
Sift4G	Benign	0.85	T
Vest4		0.043
MutPred		0.40		Gain of disorder (P = 0.2156)
MVP		0.014
MPC		0.0077
ClinPred		0.0058	T
GERP RS		-5.2
gMVP		0.24
Mutation Taster		=92/8	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: rs1059559; hg19: chr11-18291289;