chr7-30753916-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_006774.5(INMT):c.340G>A(p.Ala114Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00217 in 1,614,004 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 25 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 41 hom. )

Consequence

INMT
NM_006774.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.22

Publications

5 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00923565).

BP6

Variant 7-30753916-G-A is Benign according to our data. Variant chr7-30753916-G-A is described in ClinVar as [Benign]. Clinvar id is 783491.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0107 (1626/152288) while in subpopulation AFR AF = 0.0371 (1540/41544). AF 95% confidence interval is 0.0355. There are 25 homozygotes in GnomAd4. There are 775 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INMT	NM_006774.5 link	c.340G>A	p.Ala114Thr	missense_variant	Exon 2 of 3	ENST00000013222.5	NP_006765.4	O95050-1
INMT	NM_001199219.2 link	c.337G>A	p.Ala113Thr	missense_variant	Exon 2 of 3		NP_001186148.1	O95050-2
INMT-MINDY4	NR_037598.1 link	n.353G>A		non_coding_transcript_exon_variant	Exon 2 of 20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INMT	ENST00000013222.5 link	c.340G>A	p.Ala114Thr	missense_variant	Exon 2 of 3	1	NM_006774.5	ENSP00000013222.5		O95050-1
INMT-MINDY4	ENST00000458257.5 link	n.337G>A		non_coding_transcript_exon_variant	Exon 2 of 20	2		ENSP00000456039.1		F8WBC2

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1623

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0371

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00353

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00812

GnomAD2 exomes

AF:

0.00305

AC:

765

AN:

250816

AF XY:

0.00217

show subpopulations

Gnomad AFR exome

AF:

0.0400

Gnomad AMR exome

AF:

0.00208

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000238

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00128

AC:

1869

AN:

1461716

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

822

AN XY:

727156

show subpopulations

African (AFR)

AF:

0.0412

AC:

1380

AN:

33478

American (AMR)

AF:

0.00199

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.000116

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00229

AC:

AN:

5682

European-Non Finnish (NFE)

AF:

0.000191

AC:

212

AN:

1111970

Other (OTH)

AF:

0.00270

AC:

163

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

191

286

382

477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0107

AC:

1626

AN:

152288

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

775

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0371

AC:

1540

AN:

41544

American (AMR)

AF:

0.00353

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68020

Other (OTH)

AF:

0.00803

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

166

248

331

414

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00413

Hom.:

Bravo

AF:

0.0130

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0433

AC:

191

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00383

AC:

465

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 15, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.76

T;T

MetaRNN

Benign

0.0092

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.7

L;.

PhyloP100

4.2

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.40

N;N

REVEL

Benign

0.098

Sift

Benign

0.049

D;D

Sift4G

Uncertain

0.046

D;D

Polyphen

0.80

P;.

Vest4

0.37

MVP

0.13

MPC

0.35

ClinPred

0.023

GERP RS

3.0

Varity_R

0.24

gMVP

0.19

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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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chr7-30753916-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over