ENST00000509504.2:c.621-866G>T

Variant names:

• chr7-30882127-C-T
• NM_032222.3:c.1972-54C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000509504.2(ENSG00000250424):​c.367-54C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000250424 ENST00000509504.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.858
• Publications: 0 publications found

Genes affected

MINDY4 (HGNC:21916): (MINDY lysine 48 deubiquitinase 4) Predicted to enable Lys48-specific deubiquitinase activity. Predicted to be involved in protein K48-linked deubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000250424 (HGNC:):

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000509504.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MINDY4	NM_032222.3	MANE Select	c.1972-54C>T		intron	N/A	NP_115598.2
	INMT-MINDY4	NR_037598.1		n.2501-54C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MINDY4	ENST00000265299.6	TSL:1 MANE Select	c.1972-54C>T		intron	N/A	ENSP00000265299.6
	ENSG00000250424	ENST00000509504.2	TSL:5	c.367-54C>T		intron	N/A	ENSP00000421315.2
	INMT-MINDY4	ENST00000458257.5	TSL:2	n.*2059-54C>T		intron	N/A	ENSP00000456039.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1375948 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 676358

African (AFR) AF: 0.00 AC: 0 AN: 31218

American (AMR) AF: 0.00 AC: 0 AN: 38744

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22346

East Asian (EAS) AF: 0.00 AC: 0 AN: 38250

South Asian (SAS) AF: 0.00 AC: 0 AN: 75466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50830

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5428

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1056884

Other (OTH) AF: 0.00 AC: 0 AN: 56782

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.49
DANN	Benign	0.80
PhyloP100		-0.86

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

hg19: chr7-30921742;