Variant 11-57236577-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005161.6(APLNR):c.428G>A(p.Arg143Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,612,904 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

APLNR
NM_005161.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.06

Variant links:

Genes affected

APLNR (HGNC:339): (apelin receptor) This gene encodes a member of the G protein-coupled receptor gene family. The encoded protein is related to the angiotensin receptor, but is actually an apelin receptor that inhibits adenylate cyclase activity and plays a counter-regulatory role against the pressure action of angiotensin II by exerting hypertensive effect. It functions in the cardiovascular and central nervous systems, in glucose metabolism, in embryonic and tumor angiogenesis and as a human immunodeficiency virus (HIV-1) coreceptor. Two transcript variants resulting from alternative splicing have been identified. [provided by RefSeq, Jul 2009]

APLNR links:

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ACMG classification

Classification made for transcript

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=0.092460275).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APLNR	NM_005161.6 linkuse as main transcript	c.428G>A	p.Arg143Gln	missense_variant	1/1	ENST00000606794.2
APLNR	NR_027991.2 linkuse as main transcript	n.674G>A		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APLNR	ENST00000606794.2 linkuse as main transcript	c.428G>A	p.Arg143Gln	missense_variant	1/1		NM_005161.6	P1
APLNR	ENST00000257254.3 linkuse as main transcript	c.428G>A	p.Arg143Gln	missense_variant, NMD_transcript_variant	1/2	1

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

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:

0.00

Gnomad FIN

AF:

0.00103

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000231

AC:

AN:

247252

Hom.:

AF XY:

0.000239

AC XY:

AN XY:

134170

show subpopulations

Gnomad AFR exome

AF:

0.0000633

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000968

Gnomad NFE exome

AF:

0.000242

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.000138

AC:

201

AN:

1460672

Hom.:

Cov.:

AF XY:

0.000142

AC XY:

103

AN XY:

726688

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00121

Gnomad4 NFE exome

AF:

0.000105

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.000131

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00103

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2022

The c.428G>A (p.R143Q) alteration is located in exon 1 (coding exon 1) of the APLNR gene. This alteration results from a G to A substitution at nucleotide position 428, causing the arginine (R) at amino acid position 143 to be replaced by a glutamine (Q). 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

0.12

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.26

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.10

T;T

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.066

MetaRNN

Benign

0.092

T;T

MetaSVM

Benign

-0.49

MutationAssessor

Benign

1.7

L;L

MutationTaster

Benign

0.91

PrimateAI

Uncertain

0.69

Sift4G

Benign

0.29

T;T

Polyphen

0.76

P;P

Vest4

0.34

MVP

0.12

MPC

0.48

ClinPred

0.27

GERP RS

5.3

Varity_R

0.25

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over