rs7120555

chr11-116790206-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001371904.1(APOA5):c.1023G>C(p.Gln341His) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: APOA5 NM_001371904.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440

Genes affected

APOA5 (HGNC:17288): (apolipoprotein A5) The protein encoded by this gene is an apolipoprotein that plays an important role in regulating the plasma triglyceride levels, a major risk factor for coronary artery disease. It is a component of high density lipoprotein and is highly similar to a rat protein that is upregulated in response to liver injury. Mutations in this gene have been associated with hypertriglyceridemia and hyperlipoproteinemia type 5. This gene is located proximal to the apolipoprotein gene cluster on chromosome 11q23. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30438954).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOA5	NM_001371904.1	c.1023G>C	p.Gln341His	missense_variant	3/3	ENST00000227665.9
APOA5	NM_001166598.2	c.1023G>C	p.Gln341His	missense_variant	4/4
APOA5	NM_052968.5	c.1023G>C	p.Gln341His	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOA5	ENST00000227665.9	c.1023G>C	p.Gln341His	missense_variant	3/3	1	NM_001371904.1	P1
APOA5	ENST00000433069.2	c.1023G>C	p.Gln341His	missense_variant	4/4	1		P1
APOA5	ENST00000673688.1	c.1107G>C	p.Gln369His	missense_variant	3/3
APOA5	ENST00000542499.5	c.1023G>C	p.Gln341His	missense_variant	4/4	5		P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
Cadd	Benign	18
Dann	Uncertain	1.0
DEOGEN2	Benign	0.30	T;T
Eigen	Benign	0.19
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.52	D
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Uncertain	-0.065	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	0.83	D;D
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.8	N;N
REVEL	Uncertain	0.33
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.013	D;D
Polyphen		0.99	D;D
Vest4		0.12
MutPred		0.41		Loss of ubiquitination at K339 (P = 0.0634);Loss of ubiquitination at K339 (P = 0.0634);
MVP		0.89
MPC		1.3
ClinPred		0.89	D
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.62

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

LitVar

Other links and lift over

dbSNP: rs7120555; hg19: chr11-116660922;