Variant 7-45177416-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005856.3(RAMP3):c.166T>C(p.Trp56Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0609 in 1,614,010 control chromosomes in the GnomAD database, including 3,379 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.057 ( 322 hom., cov: 33)

Exomes 𝑓: 0.061 ( 3057 hom. )

Consequence

RAMP3
NM_005856.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.08

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043381453).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAMP3	NM_005856.3 linkuse as main transcript	c.166T>C	p.Trp56Arg	missense_variant	2/3	ENST00000242249.8
RAMP3	XM_006715631.4 linkuse as main transcript	c.499T>C	p.Trp167Arg	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
RAMP3	ENST00000242249.8 linkuse as main transcript	c.166T>C	p.Trp56Arg	missense_variant	2/3	1	NM_005856.3	P2
RAMP3	ENST00000496212.5 linkuse as main transcript	c.166T>C	p.Trp56Arg	missense_variant	2/4	4		A2
RAMP3	ENST00000481345.1 linkuse as main transcript	c.166T>C	p.Trp56Arg	missense_variant	2/4	4		P2

Frequencies

GnomAD3 genomes

AF:

0.0567

AC:

8620

AN:

152076

Hom.:

320

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0263

Gnomad AMI

AF:

0.125

Gnomad AMR

AF:

0.0910

Gnomad ASJ

AF:

0.0493

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.0766

Gnomad FIN

AF:

0.0652

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0602

Gnomad OTH

AF:

0.0689

GnomAD3 exomes

AF:

0.0662

AC:

16646

AN:

251430

Hom.:

668

AF XY:

0.0668

AC XY:

9082

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.0247

Gnomad AMR exome

AF:

0.0843

Gnomad ASJ exome

AF:

0.0467

Gnomad EAS exome

AF:

0.0977

Gnomad SAS exome

AF:

0.0736

Gnomad FIN exome

AF:

0.0646

Gnomad NFE exome

AF:

0.0615

Gnomad OTH exome

AF:

0.0670

GnomAD4 exome

AF:

0.0613

AC:

89607

AN:

1461816

Hom.:

3057

Cov.:

AF XY:

0.0618

AC XY:

44978

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0236

Gnomad4 AMR exome

AF:

0.0832

Gnomad4 ASJ exome

AF:

0.0463

Gnomad4 EAS exome

AF:

0.106

Gnomad4 SAS exome

AF:

0.0710

Gnomad4 FIN exome

AF:

0.0641

Gnomad4 NFE exome

AF:

0.0595

Gnomad4 OTH exome

AF:

0.0595

GnomAD4 genome

AF:

0.0567

AC:

8629

AN:

152194

Hom.:

322

Cov.:

AF XY:

0.0592

AC XY:

4401

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0262

Gnomad4 AMR

AF:

0.0913

Gnomad4 ASJ

AF:

0.0493

Gnomad4 EAS

AF:

0.103

Gnomad4 SAS

AF:

0.0763

Gnomad4 FIN

AF:

0.0652

Gnomad4 NFE

AF:

0.0602

Gnomad4 OTH

AF:

0.0691

Alfa

AF:

0.0624

Hom.:

821

Bravo

AF:

0.0559

TwinsUK

AF:

0.0556

AC:

206

ALSPAC

AF:

0.0602

AC:

232

ESP6500AA

AF:

0.0263

AC:

116

ESP6500EA

AF:

0.0598

AC:

514

ExAC

AF:

0.0637

AC:

7739

Asia WGS

AF:

0.0980

AC:

341

AN:

3478

EpiCase

AF:

0.0709

EpiControl

AF:

0.0696

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.57

D;T;D

Eigen

Benign

0.042

Eigen_PC

Benign

-0.077

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.51

.;T;T

MetaRNN

Benign

0.0043

T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Pathogenic

3.0

M;.;M

MutationTaster

Benign

0.023

P;P;P

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-13

D;D;D

REVEL

Benign

0.27

Sift

Uncertain

0.028

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.27

MutPred

0.33

Loss of ubiquitination at K55 (P = 0.0756);Loss of ubiquitination at K55 (P = 0.0756);Loss of ubiquitination at K55 (P = 0.0756);

MPC

0.81

ClinPred

0.13

GERP RS

1.8

Varity_R

0.68

gMVP

0.97

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over