7-30753915-C-T

Position:

chr7-30753915-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_006774.5(INMT):c.339C>T(p.Phe113Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,613,992 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 12 hom., cov: 32)

Exomes 𝑓: 0.00068 ( 11 hom. )

Consequence

INMT
NM_006774.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.28

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:

INMT (HGNC:):

INMT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 7-30753915-C-T is Benign according to our data. Variant chr7-30753915-C-T is described in ClinVar as [Benign]. Clinvar id is 722841.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.28 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00592 (901/152282) while in subpopulation AFR AF= 0.0203 (842/41534). AF 95% confidence interval is 0.0191. There are 12 homozygotes in gnomad4. There are 428 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INMT	NM_006774.5 linkuse as main transcript	c.339C>T	p.Phe113Phe	synonymous_variant	2/3	ENST00000013222.5	NP_006765.4	O95050-1
INMT	NM_001199219.2 linkuse as main transcript	c.336C>T	p.Phe112Phe	synonymous_variant	2/3		NP_001186148.1	O95050-2
INMT-MINDY4	NR_037598.1 linkuse as main transcript	n.352C>T		non_coding_transcript_exon_variant	2/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INMT	ENST00000013222.5 linkuse as main transcript	c.339C>T	p.Phe113Phe	synonymous_variant	2/3	1	NM_006774.5	ENSP00000013222.5		O95050-1
INMT-MINDY4	ENST00000458257.5 linkuse as main transcript	n.336C>T		non_coding_transcript_exon_variant	2/20	2		ENSP00000456039.1		F8WBC2

Frequencies

GnomAD3 genomes

AF:

0.00588

AC:

894

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0202

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

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:

0.000162

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00172

AC:

432

AN:

250874

Hom.:

AF XY:

0.00130

AC XY:

177

AN XY:

135662

show subpopulations

Gnomad AFR exome

AF:

0.0217

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000883

Gnomad OTH exome

AF:

0.000817

GnomAD4 exome

AF:

0.000684

AC:

1000

AN:

1461710

Hom.:

Cov.:

AF XY:

0.000612

AC XY:

445

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.0216

Gnomad4 AMR exome

AF:

0.00179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000647

Gnomad4 OTH exome

AF:

0.00174

GnomAD4 genome

AF:

0.00592

AC:

901

AN:

152282

Hom.:

Cov.:

AF XY:

0.00575

AC XY:

428

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0203

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00304

Hom.:

Bravo

AF:

0.00654

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.2

DANN

Benign

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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