chr7-30755426-C-T

Variant names:

• chr7-30755426-C-T
• rs6966017
• NM_006774.5:c.367C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_006774.5(INMT):​c.367C>T​(p.Arg123*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000798 in 1,590,878 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0043 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00043 (6 hom.)
• Consequence: INMT NM_006774.5 stop_gained
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.842
• Publications: 9 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 7-30755426-C-T is Benign according to our data. Variant chr7-30755426-C-T is described in ClinVar as Benign. ClinVar VariationId is 720371.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INMT	NM_006774.5	MANE Select	c.367C>T	p.Arg123*	stop_gained	Exon 3 of 3	NP_006765.4
	INMT	NM_001199219.2		c.364C>T	p.Arg122*	stop_gained	Exon 3 of 3	NP_001186148.1	O95050-2
	INMT-MINDY4	NR_037598.1		n.375+1488C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INMT	ENST00000013222.5	TSL:1 MANE Select	c.367C>T	p.Arg123*	stop_gained	Exon 3 of 3	ENSP00000013222.5	O95050-1
	INMT	ENST00000409539.1	TSL:1	c.364C>T	p.Arg122*	stop_gained	Exon 3 of 3	ENSP00000386961.1	O95050-2
	INMT	ENST00000484180.1	TSL:1	n.513C>T		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.00425 AC: 647 AN: 152114 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00138

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00104 AC: 230 AN: 221318 AF XY: 0.000761

Gnomad AFR exome AF: 0.0130

Gnomad AMR exome AF: 0.000724

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000403

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000590

Gnomad OTH exome AF: 0.000530

GnomAD4 exome AF: 0.000432 AC: 622 AN: 1438646 Hom.: 6 Cov.: 33 AF XY: 0.000341 AC XY: 244 AN XY: 715256

African (AFR) AF: 0.0147 AC: 489 AN: 33264

American (AMR) AF: 0.000985 AC: 43 AN: 43642

Ashkenazi Jewish (ASJ) AF: 0.0000388 AC: 1 AN: 25750

East Asian (EAS) AF: 0.000127 AC: 5 AN: 39362

South Asian (SAS) AF: 0.0000825 AC: 7 AN: 84816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38318

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5750

European-Non Finnish (NFE) AF: 0.0000271 AC: 30 AN: 1107786

Other (OTH) AF: 0.000650 AC: 39 AN: 59958

GnomAD4 genome AF: 0.00426 AC: 648 AN: 152232 Hom.: 3 Cov.: 33 AF XY: 0.00407 AC XY: 303 AN XY: 74440

African (AFR) AF: 0.0147 AC: 611 AN: 41554

American (AMR) AF: 0.00138 AC: 21 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68012

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00151 Hom.: 2

Bravo AF: 0.00426

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0111 AC: 49

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00117 AC: 142

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.00099	T
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	33
DANN	Uncertain	0.99
Eigen	Benign	-0.065
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.034	N
PhyloP100		-0.84
Vest4		0.42
GERP RS		-0.34
Mutation Taster		=179/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs6966017; hg19: chr7-30795042;