Variant rs5030980 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001138.2(AGRP):c.199G>A(p.Ala67Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0372 in 1,614,120 control chromosomes in the GnomAD database, including 1,313 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.029 ( 81 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1232 hom. )

Consequence

AGRP
NM_001138.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter P:1B:1O:1

Conservation

PhyloP100: 0.943

Variant links:

Genes affected

AGRP (HGNC:330): (agouti related neuropeptide) This gene encodes an antagonist of the melanocortin-3 and melanocortin-4 receptor. It appears to regulate hypothalamic control of feeding behavior via melanocortin receptor and/or intracellular calcium regulation, and thus plays a role in weight homeostasis. Mutations in this gene have been associated with late on-set obesity. [provided by RefSeq, Dec 2009]

AGRP links:

ATP6V0D1-DT (HGNC:55268): (ATP6V0D1 divergent transcript)

ATP6V0D1-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025504827).

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGRP	NM_001138.2 linkuse as main transcript	c.199G>A	p.Ala67Thr	missense_variant	3/4	ENST00000290953.3
ATP6V0D1-DT	NR_184227.1 linkuse as main transcript	n.127-1068C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGRP	ENST00000290953.3 linkuse as main transcript	c.199G>A	p.Ala67Thr	missense_variant	3/4	1	NM_001138.2	P1
ATP6V0D1-DT	ENST00000656196.1 linkuse as main transcript	n.207-1068C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0293

AC:

4452

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00939

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.0297

Gnomad ASJ

AF:

0.0571

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00931

Gnomad FIN

AF:

0.0374

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.0407

Gnomad OTH

AF:

0.0454

GnomAD3 exomes

AF:

0.0315

AC:

7923

AN:

251442

Hom.:

163

AF XY:

0.0322

AC XY:

4376

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00874

Gnomad AMR exome

AF:

0.0238

Gnomad ASJ exome

AF:

0.0603

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0112

Gnomad FIN exome

AF:

0.0379

Gnomad NFE exome

AF:

0.0434

Gnomad OTH exome

AF:

0.0417

GnomAD4 exome

AF:

0.0381

AC:

55641

AN:

1461808

Hom.:

1232

Cov.:

AF XY:

0.0374

AC XY:

27221

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.0109

Gnomad4 AMR exome

AF:

0.0242

Gnomad4 ASJ exome

AF:

0.0619

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0116

Gnomad4 FIN exome

AF:

0.0416

Gnomad4 NFE exome

AF:

0.0417

Gnomad4 OTH exome

AF:

0.0411

GnomAD4 genome

AF:

0.0292

AC:

4451

AN:

152312

Hom.:

Cov.:

AF XY:

0.0280

AC XY:

2088

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00943

Gnomad4 AMR

AF:

0.0297

Gnomad4 ASJ

AF:

0.0571

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00931

Gnomad4 FIN

AF:

0.0374

Gnomad4 NFE

AF:

0.0408

Gnomad4 OTH

AF:

0.0449

Alfa

AF:

0.0392

Hom.:

208

Bravo

AF:

0.0277

TwinsUK

AF:

0.0461

AC:

171

ALSPAC

AF:

0.0420

AC:

162

ESP6500AA

AF:

0.00955

AC:

ESP6500EA

AF:

0.0408

AC:

351

ExAC

AF:

0.0316

AC:

3842

Asia WGS

AF:

0.00837

AC:

AN:

3478

EpiCase

AF:

0.0429

EpiControl

AF:

0.0468

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Leanness, inherited

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 30, 2004

- -

Inherited obesity

Benign:1

Benign, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Apr 04, 2024

- -

Obesity, late-onset

Other:1

association, no assertion criteria provided

literature only

OMIM

Aug 30, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.60

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.17

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

0.74

PrimateAI

Benign

0.44

PROVEAN

Benign

0.19

REVEL

Benign

0.030

Sift

Benign

1.0

Sift4G

Benign

0.81

Polyphen

0.074

Vest4

0.045

MPC

1.1

ClinPred

0.025

GERP RS

2.5

Varity_R

0.080

gMVP

0.27

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

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