rs61741736

Variant names:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4BP6_ModerateBS1BS2

The NM_006774.5(INMT):c.791G>C(p.Ter264Serext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0289 in 1,604,138 control chromosomes in the GnomAD database, including 758 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.022 ( 52 hom., cov: 34)

Exomes 𝑓: 0.030 ( 706 hom. )

Consequence

INMT
NM_006774.5 stop_lost

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.709

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM4

Stoplost variant in NM_006774.5 Downstream stopcodon found after 268 codons.

BP6

Variant 7-30755850-G-C is Benign according to our data. Variant chr7-30755850-G-C is described in ClinVar as [Benign]. Clinvar id is 402980.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0216 (3285/152336) while in subpopulation NFE AF= 0.0343 (2332/68026). AF 95% confidence interval is 0.0331. There are 52 homozygotes in gnomad4. There are 1576 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 52 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INMT	NM_006774.5 link	c.791G>C	p.Ter264Serext*?	stop_lost	Exon 3 of 3	ENST00000013222.5	NP_006765.4	O95050-1
INMT	NM_001199219.2 link	c.788G>C	p.Ter263Serext*?	stop_lost	Exon 3 of 3		NP_001186148.1	O95050-2
INMT-MINDY4	NR_037598.1 link	n.375+1912G>C		intron_variant	Intron 2 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INMT	ENST00000013222.5 link	c.791G>C	p.Ter264Serext*?	stop_lost	Exon 3 of 3	1	NM_006774.5	ENSP00000013222.5		O95050-1
INMT-MINDY4	ENST00000458257.5 link	n.359+1912G>C		intron_variant	Intron 2 of 19	2		ENSP00000456039.1		F8WBC2

Frequencies

GnomAD3 genomes

AF:

0.0216

AC:

3285

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00596

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0158

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0163

Gnomad FIN

AF:

0.0314

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0343

Gnomad OTH

AF:

0.0186

GnomAD3 exomes

AF:

0.0224

AC:

5529

AN:

246918

Hom.:

AF XY:

0.0229

AC XY:

3058

AN XY:

133492

show subpopulations

Gnomad AFR exome

AF:

0.00489

Gnomad AMR exome

AF:

0.00955

Gnomad ASJ exome

AF:

0.00102

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0155

Gnomad FIN exome

AF:

0.0314

Gnomad NFE exome

AF:

0.0348

Gnomad OTH exome

AF:

0.0207

GnomAD4 exome

AF:

0.0297

AC:

43062

AN:

1451802

Hom.:

706

Cov.:

AF XY:

0.0293

AC XY:

21154

AN XY:

720862

show subpopulations

Gnomad4 AFR exome

AF:

0.00498

Gnomad4 AMR exome

AF:

0.00916

Gnomad4 ASJ exome

AF:

0.00131

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0148

Gnomad4 FIN exome

AF:

0.0325

Gnomad4 NFE exome

AF:

0.0343

Gnomad4 OTH exome

AF:

0.0252

GnomAD4 genome

AF:

0.0216

AC:

3285

AN:

152336

Hom.:

Cov.:

AF XY:

0.0212

AC XY:

1576

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00594

Gnomad4 AMR

AF:

0.0158

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0168

Gnomad4 FIN

AF:

0.0314

Gnomad4 NFE

AF:

0.0343

Gnomad4 OTH

AF:

0.0184

Alfa

AF:

0.0252

Hom.:

Bravo

AF:

0.0193

TwinsUK

AF:

0.0356

AC:

132

ALSPAC

AF:

0.0363

AC:

140

ESP6500AA

AF:

0.00590

AC:

ESP6500EA

AF:

0.0360

AC:

310

ExAC

AF:

0.0241

AC:

2927

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.0322

EpiControl

AF:

0.0308

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 336/13006= 2.58% -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.68

CADD

Benign

9.0

DANN

Benign

0.79

Eigen

Uncertain

0.40

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.63

Vest4

0.093

GERP RS

1.6

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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