4-164879002-T-G

Variant names:

• chr4-164879002-T-G
• rs4541465
• NM_001297550.2:c.159T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001297550.2(APELA):​c.159T>G​(p.Phe53Leu) 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. 7/11 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F53F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: APELA NM_001297550.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.953
• Publications: 5 publications found

Genes affected

APELA (HGNC:48925): (apelin receptor early endogenous ligand) This gene encodes a peptide hormone that binds to the Apelin receptor. The encoded protein is required for heart development in zebrafish and has been shown to maintain self-renewal of human embryonic stem cells through activation of the PI3K/AKT pathway. Experiments in human and mouse cell lines point to additional roles for the encoded protein in angiogenesis and regulation of vascular tone. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24550292).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297550.2. 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
	APELA	NM_001297550.2	MANE Select	c.159T>G	p.Phe53Leu	missense	Exon 2 of 3	NP_001284479.1	P0DMC3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APELA	ENST00000507152.6	TSL:1 MANE Select	c.159T>G	p.Phe53Leu	missense	Exon 2 of 3	ENSP00000484618.1	P0DMC3
	APELA	ENST00000515275.1	TSL:3	c.159T>G	p.Phe53Leu	missense	Exon 2 of 2	ENSP00000480045.1	P0DMC3
	APELA	ENST00000914507.1		c.159T>G	p.Phe53Leu	missense	Exon 2 of 3	ENSP00000584566.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Benign	0.78
DEOGEN2	Benign	0.090	T
FATHMM_MKL	Benign	0.76	D
MetaRNN	Benign	0.25	T
PhyloP100		0.95
Sift4G	Pathogenic	0.0	D
Vest4		0.49
MVP		0.32
GERP RS		3.0
Varity_R		0.12
gMVP		0.0035
Mutation Taster		=100/0	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: rs4541465; hg19: chr4-165800154;