chrX-129654584-G-T

Variant names:

• chrX-129654584-G-T
• rs757960178
• NM_017413.5:c.47C>A

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.47C>A​(p.Ser16Tyr) 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. 10/17 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)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: APLN NM_017413.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.727
• Publications: 0 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]

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=0.24870157).

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.47C>A	p.Ser16Tyr	missense	Exon 1 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.47C>A	p.Ser16Tyr	missense	Exon 1 of 3	ENSP00000391800.2	Q9ULZ1
	APLN	ENST00000865540.1		c.47C>A	p.Ser16Tyr	missense	Exon 1 of 3	ENSP00000535599.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1043389 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 338765

African (AFR) AF: 0.00 AC: 0 AN: 23926

American (AMR) AF: 0.00 AC: 0 AN: 27445

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18417

East Asian (EAS) AF: 0.00 AC: 0 AN: 26214

South Asian (SAS) AF: 0.00 AC: 0 AN: 49165

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34169

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3409

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 816685

Other (OTH) AF: 0.00 AC: 0 AN: 43959

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.36	T
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.48	T
M_CAP	Pathogenic	0.45	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.73
PrimateAI	Uncertain	0.77	T
Sift4G	Benign	0.39	T
Polyphen		0.23	B
Vest4		0.32
MutPred		0.33		Gain of helix (P = 0.0425)
MVP		0.87
ClinPred		0.52	D
GERP RS		2.1
PromoterAI		0.0063	Neutral
Varity_R		0.29
gMVP		0.14
Mutation Taster		=82/18	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: rs757960178; hg19: chrX-128788561; COSMIC: COSV100278301;