Variant 7-45177347-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000242249.8(RAMP3):c.97A>C(p.Met33Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000755 in 1,614,142 control chromosomes in the GnomAD database, including 10 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 0.0040 ( 5 hom., cov: 33)

Exomes 𝑓: 0.00042 ( 5 hom. )

Consequence

RAMP3
ENST00000242249.8 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.33

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0065813363).

BP6

Variant 7-45177347-A-C is Benign according to our data. Variant chr7-45177347-A-C is described in ClinVar as [Benign]. Clinvar id is 790591.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAMP3	NM_005856.3 linkuse as main transcript	c.97A>C	p.Met33Leu	missense_variant	2/3	ENST00000242249.8	NP_005847.1	O60896A4D2L1
RAMP3	XM_006715631.4 linkuse as main transcript	c.430A>C	p.Met144Leu	missense_variant	4/5		XP_006715694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RAMP3	ENST00000242249.8 linkuse as main transcript	c.97A>C	p.Met33Leu	missense_variant	2/3	1	NM_005856.3	ENSP00000242249.4	O60896
RAMP3	ENST00000496212.5 linkuse as main transcript	c.97A>C	p.Met33Leu	missense_variant	2/4	4		ENSP00000418460.1	J3KR56
RAMP3	ENST00000481345.1 linkuse as main transcript	c.97A>C	p.Met33Leu	missense_variant	2/4	4		ENSP00000419012.1	O60896

Frequencies

GnomAD3 genomes

AF:

0.00396

AC:

603

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0139

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00107

AC:

268

AN:

251404

Hom.:

AF XY:

0.000765

AC XY:

104

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.0137

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000421

AC:

615

AN:

1461840

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

254

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0134

Gnomad4 AMR exome

AF:

0.000939

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000585

Gnomad4 OTH exome

AF:

0.000894

GnomAD4 genome

AF:

0.00397

AC:

604

AN:

152302

Hom.:

Cov.:

AF XY:

0.00395

AC XY:

294

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0139

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000617

Hom.:

Bravo

AF:

0.00457

ESP6500AA

AF:

0.0150

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00135

AC:

164

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

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

0.083

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.31

DEOGEN2

Benign

0.10

T;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.67

.;T;T

MetaRNN

Benign

0.0066

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.97

L;.;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.68

N;N;N

REVEL

Benign

0.083

Sift

Benign

0.49

T;T;T

Sift4G

Benign

0.66

T;T;T

Polyphen

0.020

B;.;B

Vest4

0.19

MutPred

0.17

Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);

MVP

0.12

MPC

0.37

ClinPred

0.0068

GERP RS

1.8

Varity_R

0.20

gMVP

0.81

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