NM_032222.3:c.2226-1749G>C

Variant names:

• chr7-30890208-G-C
• rs6462230
• NM_032222.3:c.2226-1749G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032222.3(MINDY4):​c.2226-1749G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,212 control chromosomes in the GnomAD database, including 8,765 homozygotes. 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: 𝑓 0.26 (8765 hom., cov: 33)
• Consequence: MINDY4 NM_032222.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630
• Publications: 2 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]

OSBPL9P6 (HGNC:48736):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032222.3. 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.2226-1749G>C		intron	N/A	NP_115598.2
	INMT-MINDY4	NR_037598.1		n.2755-1749G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MINDY4	ENST00000265299.6	TSL:1 MANE Select	c.2226-1749G>C		intron	N/A	ENSP00000265299.6
	ENSG00000250424	ENST00000509504.2	TSL:5	c.620+7215G>C		intron	N/A	ENSP00000421315.2
	INMT-MINDY4	ENST00000458257.5	TSL:2	n.*2313-1749G>C		intron	N/A	ENSP00000456039.1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39224 AN: 152094 Hom.: 8737 Cov.: 33

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.0906

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.238

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.258 AC: 39312 AN: 152212 Hom.: 8765 Cov.: 33 AF XY: 0.257 AC XY: 19153 AN XY: 74428

African (AFR) AF: 0.600 AC: 24891 AN: 41504

American (AMR) AF: 0.134 AC: 2049 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 664 AN: 3466

East Asian (EAS) AF: 0.319 AC: 1656 AN: 5184

South Asian (SAS) AF: 0.338 AC: 1628 AN: 4822

European-Finnish (FIN) AF: 0.0906 AC: 962 AN: 10618

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6824 AN: 68010

Other (OTH) AF: 0.240 AC: 508 AN: 2116

Alfa AF: 0.185 Hom.: 689

Bravo AF: 0.273

Asia WGS AF: 0.336 AC: 1166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.44
DANN	Benign	0.47
PhyloP100		0.063
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs6462230; hg19: chr7-30929823;