rs10229281

Variant names:

• chr7-30837026-G-A
• rs10229281
• NM_032222.3:c.1239+262G>A

Variant summary

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

The NM_032222.3(MINDY4):​c.1239+262G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,058 control chromosomes in the GnomAD database, including 2,252 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 0.15 (2252 hom., cov: 32)
• Consequence: MINDY4 NM_032222.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 4 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]

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MINDY4	NM_032222.3	c.1239+262G>A		intron_variant	Intron 7 of 17	ENST00000265299.6	NP_115598.2
INMT-MINDY4	NR_037598.1	n.1768+262G>A		intron_variant	Intron 9 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MINDY4	ENST00000265299.6	c.1239+262G>A		intron_variant	Intron 7 of 17	1	NM_032222.3	ENSP00000265299.6
INMT-MINDY4	ENST00000458257.5	n.*1326+262G>A		intron_variant	Intron 9 of 19	2		ENSP00000456039.1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22552 AN: 151940 Hom.: 2256 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0919

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.0740

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.0917

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.148 AC: 22562 AN: 152058 Hom.: 2252 Cov.: 32 AF XY: 0.150 AC XY: 11121 AN XY: 74338

African (AFR) AF: 0.244 AC: 10127 AN: 41430

American (AMR) AF: 0.0916 AC: 1400 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 569 AN: 3468

East Asian (EAS) AF: 0.388 AC: 1996 AN: 5142

South Asian (SAS) AF: 0.214 AC: 1031 AN: 4808

European-Finnish (FIN) AF: 0.0740 AC: 785 AN: 10606

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.0918 AC: 6242 AN: 68004

Other (OTH) AF: 0.144 AC: 304 AN: 2110

Alfa AF: 0.114 Hom.: 1866

Bravo AF: 0.157

Asia WGS AF: 0.251 AC: 872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.74
PhyloP100		0.079
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10229281; hg19: chr7-30876642;