X-129648751-C-G

Variant names:

• chrX-129648751-C-G
• rs751746116
• NM_017413.5:c.109G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_017413.5(APLN):​c.109G>C​(p.Gly37Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000213 in 1,174,954 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. 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. G37S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000088 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 0.000023 (0 hom. 11 hem.)
• Consequence: APLN NM_017413.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 11 gene

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.109G>C	p.Gly37Arg	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.109G>C	p.Gly37Arg	missense	Exon 2 of 3	ENSP00000391800.2	Q9ULZ1
	APLN	ENST00000865540.1		c.394G>C	p.Gly132Arg	missense	Exon 2 of 3	ENSP00000535599.1
	ENSG00000308713	ENST00000835926.1		n.344-2772C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000884 AC: 1 AN: 113152 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000357

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000328 AC: 4 AN: 122064 AF XY: 0.0000255

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: 0.0000226 AC: 24 AN: 1061752 Hom.: 0 Cov.: 30 AF XY: 0.0000318 AC XY: 11 AN XY: 345376

African (AFR) AF: 0.00 AC: 0 AN: 25341

American (AMR) AF: 0.00 AC: 0 AN: 29345

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18709

East Asian (EAS) AF: 0.00 AC: 0 AN: 27840

South Asian (SAS) AF: 0.000459 AC: 23 AN: 50070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38055

Middle Eastern (MID) AF: 0.000251 AC: 1 AN: 3985

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 823701

Other (OTH) AF: 0.00 AC: 0 AN: 44706

GnomAD4 genome AF: 0.00000883 AC: 1 AN: 113202 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 35352

African (AFR) AF: 0.00 AC: 0 AN: 31256

American (AMR) AF: 0.00 AC: 0 AN: 10839

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2654

East Asian (EAS) AF: 0.00 AC: 0 AN: 3572

South Asian (SAS) AF: 0.000359 AC: 1 AN: 2789

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6295

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53343

Other (OTH) AF: 0.00 AC: 0 AN: 1551

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000179 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.94	T
PhyloP100		1.1
PrimateAI	Uncertain	0.54	T
Sift4G	Uncertain	0.030	D
Polyphen		0.96	D
Vest4		0.76
MutPred		0.30		Gain of solvent accessibility (P = 0.0037)
MVP		0.62
ClinPred		0.54	D
GERP RS		3.9
Varity_R		0.22
gMVP		0.11
Mutation Taster		=86/14	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: rs751746116; hg19: chrX-128782728;