chr6-142078884-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002511.4(NMBR):āc.442C>Gā(p.Pro148Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000473 in 1,612,236 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00034 ( 0 hom., cov: 31)
Exomes š: 0.00049 ( 1 hom. )
Consequence
NMBR
NM_002511.4 missense
NM_002511.4 missense
Scores
10
7
2
Clinical Significance
Conservation
PhyloP100: 9.60
Genes affected
NMBR (HGNC:7843): (neuromedin B receptor) This gene encodes a 7-transmembrane G protein-coupled receptor that binds neuromedin B, which is a growth factor and mitogen for gastrointestinal epithelial tissue and for normal and neoplastic lung. This receptor may play a role in smooth muscle contraction, neuronal responses, and the regulation of cell growth. Antagonists of this receptor have a potential therapeutic use in inhibiting tumor cell growth. Polymorphisms in this gene may be associated with a susceptibility for schizophrenia. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NMBR | NM_002511.4 | c.442C>G | p.Pro148Ala | missense_variant | 3/4 | ENST00000258042.2 | |
NMBR | NM_001324307.2 | c.-3C>G | 5_prime_UTR_variant | 3/4 | |||
NMBR | NM_001324308.2 | c.-3C>G | 5_prime_UTR_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NMBR | ENST00000258042.2 | c.442C>G | p.Pro148Ala | missense_variant | 3/4 | 1 | NM_002511.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000337 AC: 51AN: 151254Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000472 AC: 117AN: 247778Hom.: 0 AF XY: 0.000410 AC XY: 55AN XY: 134074
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GnomAD4 exome AF: 0.000487 AC: 712AN: 1460864Hom.: 1 Cov.: 31 AF XY: 0.000498 AC XY: 362AN XY: 726642
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GnomAD4 genome AF: 0.000337 AC: 51AN: 151372Hom.: 0 Cov.: 31 AF XY: 0.000325 AC XY: 24AN XY: 73900
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 19, 2022 | The c.442C>G (p.P148A) alteration is located in exon 2 (coding exon 2) of the NMBR gene. This alteration results from a C to G substitution at nucleotide position 442, causing the proline (P) at amino acid position 148 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at