X-129648771-T-C

Position:

• chrX-129648771-T-C

Variant summary

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

The NM_017413.5(APLN):​c.89A>G​(p.Asp30Gly) 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. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: APLN NM_017413.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.14

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]

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=0.10152012).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APLN	NM_017413.5	c.89A>G	p.Asp30Gly	missense_variant	2/3	ENST00000429967.3	NP_059109.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APLN	ENST00000429967.3	c.89A>G	p.Asp30Gly	missense_variant	2/3	1	NM_017413.5	ENSP00000391800.2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2023

The c.89A>G (p.D30G) alteration is located in exon 2 (coding exon 2) of the APLN gene. This alteration results from a A to G substitution at nucleotide position 89, causing the aspartic acid (D) at amino acid position 30 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	10
DANN	Benign	0.96
DEOGEN2	Benign	0.39	T
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.49	T
Sift4G	Benign	0.063	T
Polyphen		0.0010	B
Vest4		0.24
MutPred		0.27		Loss of solvent accessibility (P = 0.1177);
MVP		0.33
ClinPred		0.080	T
GERP RS		3.1
Varity_R		0.23
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-128782748;