chr7-30753915-C-T

Variant names:

• chr7-30753915-C-T
• rs116690173
• NM_006774.5:c.339C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.28
• Publications: 3 publications found

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-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]

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INMT	NM_006774.5	c.339C>T	p.Phe113Phe	synonymous_variant	Exon 2 of 3	ENST00000013222.5	NP_006765.4
INMT	NM_001199219.2	c.336C>T	p.Phe112Phe	synonymous_variant	Exon 2 of 3		NP_001186148.1
INMT-MINDY4	NR_037598.1	n.352C>T		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	c.339C>T	p.Phe113Phe	synonymous_variant	Exon 2 of 3	1	NM_006774.5	ENSP00000013222.5
INMT-MINDY4	ENST00000458257.5	n.336C>T		non_coding_transcript_exon_variant	Exon 2 of 20	2		ENSP00000456039.1

Frequencies

GnomAD3 genomes AF: 0.00588 AC: 894 AN: 152164 Hom.: 12 Cov.: 32

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

GnomAD2 exomes AF: 0.00172 AC: 432 AN: 250874 AF XY: 0.00130

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 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.: 11 Cov.: 32 AF XY: 0.000612 AC XY: 445 AN XY: 727154

African (AFR) AF: 0.0216 AC: 724 AN: 33474

American (AMR) AF: 0.00179 AC: 80 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00229 AC: 13 AN: 5682

European-Non Finnish (NFE) AF: 0.0000647 AC: 72 AN: 1111972

Other (OTH) AF: 0.00174 AC: 105 AN: 60374

GnomAD4 genome AF: 0.00592 AC: 901 AN: 152282 Hom.: 12 Cov.: 32 AF XY: 0.00575 AC XY: 428 AN XY: 74452

African (AFR) AF: 0.0203 AC: 842 AN: 41534

American (AMR) AF: 0.00216 AC: 33 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68012

Other (OTH) AF: 0.00614 AC: 13 AN: 2116

Alfa AF: 0.00304 Hom.: 2

Bravo AF: 0.00654

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 20, 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
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.2
DANN	Benign	0.63
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs116690173; hg19: chr7-30793531; COSMIC: COSV104532471;