rs12669187

Variant names:

• chr7-30875863-G-A
• rs12669187
• NM_032222.3:c.1971+207G>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.1971+207G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0714 in 152,254 control chromosomes in the GnomAD database, including 631 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 0.071 (631 hom., cov: 32)
• Consequence: MINDY4 NM_032222.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MINDY4	NM_032222.3	c.1971+207G>A		intron_variant	Intron 15 of 17	ENST00000265299.6	NP_115598.2
INMT-MINDY4	NR_037598.1	n.2500+207G>A		intron_variant	Intron 17 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MINDY4	ENST00000265299.6	c.1971+207G>A		intron_variant	Intron 15 of 17	1	NM_032222.3	ENSP00000265299.6
ENSG00000250424	ENST00000509504.2	c.366+207G>A		intron_variant	Intron 5 of 10	5		ENSP00000421315.2
INMT-MINDY4	ENST00000458257.5	n.*2058+207G>A		intron_variant	Intron 17 of 19	2		ENSP00000456039.1
MINDY4	ENST00000409881.1	n.1804+207G>A		intron_variant	Intron 3 of 5	2

Frequencies

GnomAD3 genomes AF: 0.0712 AC: 10833 AN: 152136 Hom.: 622 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0311

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.0931

Gnomad FIN AF: 0.0433

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.0355

Gnomad OTH AF: 0.0603

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

GnomAD4 genome AF: 0.0714 AC: 10875 AN: 152254 Hom.: 631 Cov.: 32 AF XY: 0.0719 AC XY: 5351 AN XY: 74460

African (AFR) AF: 0.148 AC: 6159 AN: 41526

American (AMR) AF: 0.0311 AC: 476 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 162 AN: 3468

East Asian (EAS) AF: 0.110 AC: 571 AN: 5186

South Asian (SAS) AF: 0.0932 AC: 449 AN: 4818

European-Finnish (FIN) AF: 0.0433 AC: 459 AN: 10610

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.0355 AC: 2418 AN: 68024

Other (OTH) AF: 0.0625 AC: 132 AN: 2112

Alfa AF: 0.0439 Hom.: 348

Bravo AF: 0.0725

Asia WGS AF: 0.107 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0090
DANN	Benign	0.57
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs12669187; hg19: chr7-30915478;