APOA1 p.Phe253Phe

Variant names:

• chr11-116835852-G-G
• NM_000039.3:c.

Your query was ambiguous. Multiple possible variants found:

• chr11-116835853--
• chr11-116835853-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000039.3(APOA1):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: APOA1 NM_000039.3 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.173
• Publications: 0 publications found

Genes affected

APOA1 (HGNC:600): (apolipoprotein A1) This gene encodes apolipoprotein A-I, which is the major protein component of high density lipoprotein (HDL) in plasma. The encoded preproprotein is proteolytically processed to generate the mature protein, which promotes cholesterol efflux from tissues to the liver for excretion, and is a cofactor for lecithin cholesterolacyltransferase (LCAT), an enzyme responsible for the formation of most plasma cholesteryl esters. This gene is closely linked with two other apolipoprotein genes on chromosome 11. Defects in this gene are associated with HDL deficiencies, including Tangier disease, and with systemic non-neuropathic amyloidosis. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein. [provided by RefSeq, Dec 2015]

APOA1 Gene-Disease associations (from GenCC):

• familial visceral amyloidosis

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hypoalphalipoproteinemia, primary, 2

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• AApoAI amyloidosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• apolipoprotein A-I deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000039.3. 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
	APOA1	NM_000039.3	MANE Select	c.		exon_region	Exon 4 of 4	NP_000030.1	A0A024R3E3
	APOA1	NM_001318017.2		c.		exon_region	Exon 4 of 4	NP_001304946.1	A0A024R3E3
	APOA1	NM_001318018.2		c.		exon_region	Exon 4 of 4	NP_001304947.1	P02647

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOA1	ENST00000236850.5	TSL:1 MANE Select	c.		exon_region	Exon 4 of 4	ENSP00000236850.3	P02647
	APOA1	ENST00000375323.5	TSL:1	c.		exon_region	Exon 3 of 3	ENSP00000364472.1	P02647
	APOA1	ENST00000855312.1		c.		exon_region	Exon 4 of 4	ENSP00000525371.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.17

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-116706568;