NM_005855.4:c.43C>G

Variant summary

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

The NM_005855.4(RAMP1):​c.43C>G​(p.Leu15Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

RAMP1
NM_005855.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.372
Variant links:
Genes affected
RAMP1 (HGNC:9843): (receptor activity modifying protein 1) 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 (RAMP1) protein, CRLR functions as a CGRP receptor. The RAMP1 protein is involved in the terminal glycosylation, maturation, and presentation of the CGRP receptor to the cell surface. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

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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=0.13503698).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAMP1NM_005855.4 linkc.43C>G p.Leu15Val missense_variant Exon 1 of 3 ENST00000254661.5 NP_005846.1 O60894

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAMP1ENST00000254661.5 linkc.43C>G p.Leu15Val missense_variant Exon 1 of 3 1 NM_005855.4 ENSP00000254661.4 O60894
RAMP1ENST00000409726 linkc.-85C>G 5_prime_UTR_variant Exon 1 of 4 3 ENSP00000386720.1 E9PC20
RAMP1ENST00000404910.6 linkc.-15+591C>G intron_variant Intron 1 of 2 2 ENSP00000384688.2 E9PC20

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 11, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.43C>G (p.L15V) alteration is located in exon 1 (coding exon 1) of the RAMP1 gene. This alteration results from a C to G substitution at nucleotide position 43, causing the leucine (L) at amino acid position 15 to be replaced by a valine (V). 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
0.11
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
21
DANN
Benign
0.97
DEOGEN2
Benign
0.25
T
Eigen
Benign
-0.42
Eigen_PC
Benign
-0.34
FATHMM_MKL
Benign
0.52
D
LIST_S2
Benign
0.57
T
M_CAP
Uncertain
0.17
D
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.90
L
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-0.89
N
REVEL
Benign
0.0090
Sift
Benign
0.038
D
Sift4G
Benign
0.16
T
Polyphen
0.020
B
Vest4
0.27
MutPred
0.32
Gain of MoRF binding (P = 0.0801);
MVP
0.099
MPC
0.013
ClinPred
0.10
T
GERP RS
1.7
Varity_R
0.14
gMVP
0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-238768361; API