chr7-30755422-C-T

Variant names:

• chr7-30755422-C-T
• rs201848016
• NM_006774.5:c.363C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_006774.5(INMT):​c.363C>T​(p.Ser121Ser) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000706 in 1,585,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000052 (0 hom.)
• Consequence: INMT NM_006774.5 splice_region, synonymous
• Scores: Splicing: ADA: 0.00008728
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.48
• Publications: 1 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 7-30755422-C-T is Benign according to our data. Variant chr7-30755422-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3860547.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.48 with no splicing effect.

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.363C>T	p.Ser121Ser	splice_region synonymous	Exon 3 of 3	NP_006765.4
	INMT	NM_001199219.2		c.360C>T	p.Ser120Ser	splice_region synonymous	Exon 3 of 3	NP_001186148.1	O95050-2
	INMT-MINDY4	NR_037598.1		n.375+1484C>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.363C>T	p.Ser121Ser	splice_region synonymous	Exon 3 of 3	ENSP00000013222.5	O95050-1
	INMT	ENST00000409539.1	TSL:1	c.360C>T	p.Ser120Ser	splice_region synonymous	Exon 3 of 3	ENSP00000386961.1	O95050-2
	INMT	ENST00000484180.1	TSL:1	n.509C>T		splice_region non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 152170 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000117 AC: 25 AN: 212820 AF XY: 0.000129

Gnomad AFR exome AF: 0.000581

Gnomad AMR exome AF: 0.000124

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000238

Gnomad FIN exome AF: 0.000200

Gnomad NFE exome AF: 0.0000206

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000523 AC: 75 AN: 1433422 Hom.: 0 Cov.: 33 AF XY: 0.0000674 AC XY: 48 AN XY: 712278

African (AFR) AF: 0.000634 AC: 21 AN: 33114

American (AMR) AF: 0.0000931 AC: 4 AN: 42962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25532

East Asian (EAS) AF: 0.000281 AC: 11 AN: 39126

South Asian (SAS) AF: 0.000250 AC: 21 AN: 83964

European-Finnish (FIN) AF: 0.0000263 AC: 1 AN: 38024

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.0000109 AC: 12 AN: 1105214

Other (OTH) AF: 0.0000837 AC: 5 AN: 59748

GnomAD4 genome AF: 0.000243 AC: 37 AN: 152288 Hom.: 0 Cov.: 33 AF XY: 0.000228 AC XY: 17 AN XY: 74468

African (AFR) AF: 0.000674 AC: 28 AN: 41558

American (AMR) AF: 0.000327 AC: 5 AN: 15300

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4818

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000137 Hom.: 0

Bravo AF: 0.000257

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.16
DANN	Benign	0.91
PhyloP100		-2.5
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000087
dbscSNV1_RF	Benign	0.0060
SpliceAI score (max)		0.020		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: rs201848016; hg19: chr7-30795038;