Genetic Variant NM_006774.5:c.98C>A (chr7-30752248-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006774.5(INMT):c.98C>A(p.Pro33His) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

INMT
NM_006774.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19

Publications

0 publications found

Variant links:

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]

INMT links:

INMT-MINDY4 (HGNC:41995): (INMT-MINDY4 readthrough (NMD candidate)) This locus represents rare but naturally occurring read-through transcription between the INMT (indolethylamine N-methyltransferase) and FAM188B (family with sequence similarity 188, member B) genes on chromosome 7. The read-through transcript is unlikely to produce a protein because it is a nonsense-mediated mRNA decay (NMD) candidate based on translation from the supported INMT start codon. [provided by RefSeq, Nov 2010]

INMT-MINDY4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17917144).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006774.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
INMT	NM_006774.5	MANE Select	c.98C>A	p.Pro33His	missense	Exon 1 of 3	NP_006765.4
INMT	NM_001199219.2		c.98C>A	p.Pro33His	missense	Exon 1 of 3	NP_001186148.1	O95050-2
INMT-MINDY4	NR_037598.1		n.114C>A		non_coding_transcript_exon	Exon 1 of 20

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
INMT	ENST00000013222.5	TSL:1 MANE Select	c.98C>A	p.Pro33His	missense	Exon 1 of 3	ENSP00000013222.5	O95050-1
INMT	ENST00000409539.1	TSL:1	c.98C>A	p.Pro33His	missense	Exon 1 of 3	ENSP00000386961.1	O95050-2
INMT-MINDY4	ENST00000458257.5	TSL:2	n.98C>A		non_coding_transcript_exon	Exon 1 of 20	ENSP00000456039.1	F8WBC2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0082

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.42

M_CAP

Benign

0.0029

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

1.2

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.0

REVEL

Benign

0.075

Sift

Uncertain

0.013

Sift4G

Benign

0.11

Polyphen

1.0

Vest4

0.24

MutPred

0.32

Gain of catalytic residue at P33 (P = 0.1009)

MVP

0.33

MPC

0.64

ClinPred

0.35

GERP RS

3.1

PromoterAI

-0.020

Neutral

(source)

Varity_R

0.31

gMVP

0.12

Mutation Taster

=87/13

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over