rs4541465

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr4-164879002-T-A
• chr4-164879002-T-C
• chr4-164879002-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001297550.2(APELA):​c.159T>A​(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.

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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24678895).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APELA	NM_001297550.2	c.159T>A	p.Phe53Leu	missense_variant	Exon 2 of 3	ENST00000507152.6	NP_001284479.1
APELA	XM_017007623.2	c.159T>A	p.Phe53Leu	missense_variant	Exon 2 of 3		XP_016863112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APELA	ENST00000507152.6	c.159T>A	p.Phe53Leu	missense_variant	Exon 2 of 3	1	NM_001297550.2	ENSP00000484618.1
APELA	ENST00000515275.1	c.159T>A	p.Phe53Leu	missense_variant	Exon 2 of 2	3		ENSP00000480045.1
APELA	ENST00000510062.5	n.159T>A		non_coding_transcript_exon_variant	Exon 2 of 4	3		ENSP00000478306.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Benign	0.79
DEOGEN2	Benign	0.090	T;T
FATHMM_MKL	Benign	0.75	D
MetaRNN	Benign	0.25	T;T
Sift4G	Pathogenic	0.0	D;D
Vest4		0.49
MVP		0.32
GERP RS		3.0
Varity_R		0.12
gMVP		0.0035

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: rs4541465; hg19: chr4-165800154;