chrX-129654584-G-A

Variant names:

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

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>T​(p.Ser16Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000173 in 1,155,674 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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. S16Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 9.6e-7 (0 hom. 0 hem.)
• Consequence: APLN NM_017413.5 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.095540434).

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>T	p.Ser16Phe	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>T	p.Ser16Phe	missense	Exon 1 of 3	ENSP00000391800.2	Q9ULZ1
	APLN	ENST00000865540.1		c.47C>T	p.Ser16Phe	missense	Exon 1 of 3	ENSP00000535599.1

Frequencies

GnomAD3 genomes AF: 0.00000891 AC: 1 AN: 112237 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000322

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 91966 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.58e-7 AC: 1 AN: 1043390 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 338766

African (AFR) AF: 0.0000418 AC: 1 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: 34170

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 AF: 0.00000891 AC: 1 AN: 112284 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 34520

African (AFR) AF: 0.0000322 AC: 1 AN: 31075

American (AMR) AF: 0.00 AC: 0 AN: 10841

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3495

South Asian (SAS) AF: 0.00 AC: 0 AN: 2782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6151

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 215

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52879

Other (OTH) AF: 0.00 AC: 0 AN: 1530

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.35	T
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.73
PrimateAI	Uncertain	0.75	T
Sift4G	Benign	0.32	T
Polyphen		0.0010	B
Vest4		0.14
MutPred		0.33		Gain of helix (P = 0.0425)
MVP		0.87
ClinPred		0.59	D
GERP RS		2.1
PromoterAI		0.020	Neutral
Varity_R		0.21
gMVP		0.15
Mutation Taster		=83/17	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;