Variant 7-45177327-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005856.3(RAMP3):c.77G>A(p.Gly26Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00539 in 1,614,158 control chromosomes in the GnomAD database, including 386 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.028 ( 213 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 173 hom. )

Consequence

RAMP3
NM_005856.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0180

Variant links:

Genes affected

RAMP3 (HGNC:9845): (receptor activity modifying protein 3) The protein encoded by this gene is a member of the RAMP family of single-transmembrane-domain proteins, called receptor (calcitonin) activity modifying proteins (RAMPs). RAMPs are type I transmembrane proteins with an extracellular N terminus and a cytoplasmic C terminus. RAMPs are required to transport calcitonin-receptor-like receptor (CRLR) to the plasma membrane. CRLR, a receptor with seven transmembrane domains, can function as either a calcitonin-gene-related peptide (CGRP) receptor or an adrenomedullin receptor, depending on which members of the RAMP family are expressed. In the presence of this (RAMP3) protein, CRLR functions as an adrenomedullin receptor. [provided by RefSeq, Jul 2008]

RAMP3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002192974).

BP6

Variant 7-45177327-G-A is Benign according to our data. Variant chr7-45177327-G-A is described in ClinVar as [Benign]. Clinvar id is 792073.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAMP3	NM_005856.3 linkuse as main transcript	c.77G>A	p.Gly26Asp	missense_variant	2/3	ENST00000242249.8	NP_005847.1
RAMP3	XM_006715631.4 linkuse as main transcript	c.410G>A	p.Gly137Asp	missense_variant	4/5		XP_006715694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RAMP3	ENST00000242249.8 linkuse as main transcript	c.77G>A	p.Gly26Asp	missense_variant	2/3	1	NM_005856.3	ENSP00000242249	P2
RAMP3	ENST00000496212.5 linkuse as main transcript	c.77G>A	p.Gly26Asp	missense_variant	2/4	4		ENSP00000418460	A2
RAMP3	ENST00000481345.1 linkuse as main transcript	c.77G>A	p.Gly26Asp	missense_variant	2/4	4		ENSP00000419012	P2

Frequencies

GnomAD3 genomes

AF:

0.0280

AC:

4269

AN:

152216

Hom.:

214

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0978

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00896

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.00785

AC:

1973

AN:

251378

Hom.:

AF XY:

0.00576

AC XY:

783

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.104

Gnomad AMR exome

AF:

0.00512

Gnomad ASJ exome

AF:

0.00268

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000475

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00302

AC:

4422

AN:

1461824

Hom.:

173

Cov.:

AF XY:

0.00269

AC XY:

1957

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.101

Gnomad4 AMR exome

AF:

0.00537

Gnomad4 ASJ exome

AF:

0.00245

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000272

Gnomad4 OTH exome

AF:

0.00664

GnomAD4 genome

AF:

0.0281

AC:

4274

AN:

152334

Hom.:

213

Cov.:

AF XY:

0.0265

AC XY:

1972

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0976

Gnomad4 AMR

AF:

0.00895

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.00542

Hom.:

Bravo

AF:

0.0324

ESP6500AA

AF:

0.0928

AC:

409

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.00949

AC:

1152

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 03, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.63

CADD

Benign

5.6

DANN

Benign

0.45

DEOGEN2

Benign

0.11

T;T;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.54

.;T;T

MetaRNN

Benign

0.0022

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

N;.;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.71

PROVEAN

Benign

0.58

N;N;N

REVEL

Benign

0.022

Sift

Benign

0.62

T;T;T

Sift4G

Benign

0.55

T;T;T

Polyphen

0.0030

B;.;B

Vest4

0.21

MVP

0.30

MPC

0.43

ClinPred

0.0016

GERP RS

2.4

Varity_R

0.045

gMVP

0.65

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