rs77743549
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_006774.5(INMT):āc.137A>Cā(p.His46Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0077 in 1,613,830 control chromosomes in the GnomAD database, including 84 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.
Frequency
Genomes: š 0.0063 ( 10 hom., cov: 32)
Exomes š: 0.0078 ( 74 hom. )
Consequence
INMT
NM_006774.5 missense
NM_006774.5 missense
Scores
1
2
15
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.964
Genes affected
INMT (HGNC:6069): (indolethylamine N-methyltransferase) N-methylation of endogenous and xenobiotic compounds is a major method by which they are degraded. This gene encodes an enzyme that N-methylates indoles such as tryptamine. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream MINDY4 (aka FAM188B) gene. In rodents and other mammals such as cetartiodactyla this gene is in the opposite orientation compared to its orientation in human and other primates and this gene appears to have been lost in carnivora and chiroptera. [provided by RefSeq, Jul 2019]
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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=0.0071540475).
BS1
?
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00784 (11458/1461580) while in subpopulation EAS AF= 0.0205 (815/39698). AF 95% confidence interval is 0.0194. There are 74 homozygotes in gnomad4_exome. There are 5627 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 10 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INMT | NM_006774.5 | c.137A>C | p.His46Pro | missense_variant | 1/3 | ENST00000013222.5 | |
INMT-MINDY4 | NR_037598.1 | n.153A>C | non_coding_transcript_exon_variant | 1/20 | |||
INMT | NM_001199219.2 | c.137A>C | p.His46Pro | missense_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INMT | ENST00000013222.5 | c.137A>C | p.His46Pro | missense_variant | 1/3 | 1 | NM_006774.5 | P4 | |
INMT | ENST00000409539.1 | c.137A>C | p.His46Pro | missense_variant | 1/3 | 1 | A1 | ||
INMT | ENST00000484180.1 | n.301-1444A>C | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00633 AC: 963AN: 152132Hom.: 10 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.00758 AC: 1905AN: 251386Hom.: 10 AF XY: 0.00786 AC XY: 1068AN XY: 135882
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GnomAD4 exome AF: 0.00784 AC: 11458AN: 1461580Hom.: 74 Cov.: 33 AF XY: 0.00774 AC XY: 5627AN XY: 727134
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GnomAD4 genome ? AF: 0.00633 AC: 963AN: 152250Hom.: 10 Cov.: 32 AF XY: 0.00660 AC XY: 491AN XY: 74448
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27
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28
ESP6500AA
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1
ESP6500EA
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67
ExAC
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1000
Asia WGS
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3478
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ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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