Variant summary

Our verdict is Benign. The variant received -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

Publications

10 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 52 AR gene

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
INMT	NM_006774.5	MANE Select	c.791G>C	p.Ter264Serext*?	stop_lost	Exon 3 of 3	NP_006765.4
INMT	NM_001199219.2		c.788G>C	p.Ter263Serext*?	stop_lost	Exon 3 of 3	NP_001186148.1
INMT-MINDY4	NR_037598.1		n.375+1912G>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
INMT	ENST00000013222.5	TSL:1 MANE Select	c.791G>C	p.Ter264Serext*?	stop_lost	Exon 3 of 3	ENSP00000013222.5
INMT	ENST00000409539.1	TSL:1	c.788G>C	p.Ter263Serext*?	stop_lost splice_region	Exon 3 of 3	ENSP00000386961.1
INMT	ENST00000484180.1	TSL:1	n.937G>C		non_coding_transcript_exon	Exon 4 of 4

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

GnomAD2 exomes

AF:

0.0224

AC:

5529

AN:

246918

AF XY:

0.0229

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 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

African (AFR)

AF:

0.00498

AC:

166

AN:

33322

American (AMR)

AF:

0.00916

AC:

408

AN:

44530

Ashkenazi Jewish (ASJ)

AF:

0.00131

AC:

AN:

25866

East Asian (EAS)

AF:

0.000101

AC:

AN:

39524

South Asian (SAS)

AF:

0.0148

AC:

1270

AN:

85858

European-Finnish (FIN)

AF:

0.0325

AC:

1656

AN:

50946

Middle Eastern (MID)

AF:

0.00905

AC:

AN:

5414

European-Non Finnish (NFE)

AF:

0.0343

AC:

37963

AN:

1106402

Other (OTH)

AF:

0.0252

AC:

1512

AN:

59940

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

2294

4588

6882

9176

11470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1384

2768

4152

5536

6920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0216

AC:

3285

AN:

152336

Hom.:

Cov.:

AF XY:

0.0212

AC XY:

1576

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00594

AC:

247

AN:

41576

American (AMR)

AF:

0.0158

AC:

242

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.0168

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0314

AC:

333

AN:

10622

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0343

AC:

2332

AN:

68026

Other (OTH)

AF:

0.0184

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

166

332

498

664

830

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions as Germline

Significance:Benign

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

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.68

CADD

Benign

9.0

(source)

DANN

Benign

0.79

Eigen

Uncertain

0.40

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.63

PhyloP100

0.71

Vest4

0.093

GERP RS

1.6

Mutation Taster

=86/114

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs61741736

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over