chrX-129648697-A-C

Variant names:

• chrX-129648697-A-C
• rs757193827
• NM_017413.5:c.163T>G

Variant summary

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

The NM_017413.5(APLN):​c.163T>G​(p.Trp55Gly) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W55R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 24)
• Consequence: APLN NM_017413.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.57
• Publications: 1 publications found

Genes affected

APLN (HGNC:16665): (apelin) This gene encodes a peptide that functions as an endogenous ligand for the G-protein coupled apelin receptor. The encoded preproprotein is proteolytically processed into biologically active C-terminal peptide fragments. These peptide fragments activate different tissue specific signaling pathways that regulate diverse biological functions including fluid homeostasis, cardiovascular function and insulin secretion. This protein also functions as a coreceptor for the human immunodeficiency virus 1. [provided by RefSeq, Feb 2016]

ENSG00000308713 (HGNC:):

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=0.24620217).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017413.5. 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
	APLN	NM_017413.5	MANE Select	c.163T>G	p.Trp55Gly	missense	Exon 2 of 3	NP_059109.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APLN	ENST00000429967.3	TSL:1 MANE Select	c.163T>G	p.Trp55Gly	missense	Exon 2 of 3	ENSP00000391800.2	Q9ULZ1
	APLN	ENST00000865540.1		c.448T>G	p.Trp150Gly	missense	Exon 2 of 3	ENSP00000535599.1
	ENSG00000308713	ENST00000835926.1		n.344-2826A>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.41	T
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
PhyloP100		3.6
PrimateAI	Uncertain	0.57	T
Sift4G	Benign	0.23	T
Polyphen		0.73	P
Vest4		0.51
MutPred		0.27		Gain of relative solvent accessibility (P = 0.005)
MVP		0.65
ClinPred		0.93	D
GERP RS		4.5
Varity_R		0.62
gMVP		0.050
Mutation Taster		=78/22	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: rs757193827; hg19: chrX-128782674;