X-129647887-C-T

Variant names:

• chrX-129647887-C-T
• rs3115758
• NM_017413.5:c.*36G>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.*36G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000115 in 869,537 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.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000012 (0 hom. 0 hem.)
• Consequence: APLN NM_017413.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550
• 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]

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 (REVEL=0.022).

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.*36G>A		3_prime_UTR	Exon 3 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.*36G>A		3_prime_UTR	Exon 3 of 3	ENSP00000391800.2
	APLN	ENST00000865540.1		c.*36G>A		3_prime_UTR	Exon 3 of 3	ENSP00000535599.1
	ENSG00000308713	ENST00000835926.1		n.344-3636C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000115 AC: 1 AN: 869537 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 282363

African (AFR) AF: 0.00 AC: 0 AN: 19300

American (AMR) AF: 0.00 AC: 0 AN: 22268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11951

East Asian (EAS) AF: 0.00 AC: 0 AN: 9709

South Asian (SAS) AF: 0.00 AC: 0 AN: 47696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20905

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3141

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 702759

Other (OTH) AF: 0.0000314 AC: 1 AN: 31808

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.17
DANN	Benign	0.76
PhyloP100		-0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs3115758; hg19: chrX-128781864;