rs762779755

Variant names:

• chr7-30752293-C-T
• rs762779755
• NM_006774.5:c.143C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-30752293-C-T
• chr7-30752293-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006774.5(INMT):​c.143C>T​(p.Thr48Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: INMT NM_006774.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.650
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23061544).

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.143C>T	p.Thr48Ile	missense	Exon 1 of 3	NP_006765.4
	INMT	NM_001199219.2		c.143C>T	p.Thr48Ile	missense	Exon 1 of 3	NP_001186148.1	O95050-2
	INMT-MINDY4	NR_037598.1		n.159C>T		non_coding_transcript_exon	Exon 1 of 20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INMT	ENST00000013222.5	TSL:1 MANE Select	c.143C>T	p.Thr48Ile	missense	Exon 1 of 3	ENSP00000013222.5	O95050-1
	INMT	ENST00000409539.1	TSL:1	c.143C>T	p.Thr48Ile	missense	Exon 1 of 3	ENSP00000386961.1	O95050-2
	INMT-MINDY4	ENST00000458257.5	TSL:2	n.143C>T		non_coding_transcript_exon	Exon 1 of 20	ENSP00000456039.1	F8WBC2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461664 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727142

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111914

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.057
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.65
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.10
Sift	Benign	0.42	T
Sift4G	Benign	0.17	T
Polyphen		0.98	D
Vest4		0.20
MutPred		0.57		Gain of catalytic residue at T48 (P = 0.0551)
MVP		0.32
MPC		0.71
ClinPred		0.98	D
GERP RS		2.8
PromoterAI		0.025	Neutral
Varity_R		0.25
gMVP		0.13
Mutation Taster		=81/19	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: rs762779755; hg19: chr7-30791909;