15-58771525-T-A

Variant names:

• chr15-58771525-T-A
• rs1037468456
• NM_001040450.3:c.130T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001040450.3(MINDY2):​c.130T>A​(p.Trp44Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: MINDY2 NM_001040450.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.458
• Publications: 0 publications found

Genes affected

MINDY2 (HGNC:26954): (MINDY lysine 48 deubiquitinase 2) Enables cysteine-type peptidase activity and polyubiquitin modification-dependent protein binding activity. Predicted to be involved in protein K48-linked deubiquitination. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MINDY2-DT (HGNC:55889): (MINDY2 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040450.3. 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
	MINDY2	NM_001040450.3	MANE Select	c.130T>A	p.Trp44Arg	missense	Exon 1 of 9	NP_001035540.1	Q8NBR6-1
	MINDY2	NM_001040453.3		c.130T>A	p.Trp44Arg	missense	Exon 1 of 9	NP_001035543.1	Q8NBR6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MINDY2	ENST00000559228.6	TSL:2 MANE Select	c.130T>A	p.Trp44Arg	missense	Exon 1 of 9	ENSP00000452885.1	Q8NBR6-1
	MINDY2	ENST00000450403.3	TSL:1	c.130T>A	p.Trp44Arg	missense	Exon 1 of 9	ENSP00000393231.2	Q8NBR6-2
	MINDY2	ENST00000316848.9	TSL:1	n.130T>A		non_coding_transcript_exon	Exon 1 of 8	ENSP00000326194.5	J3KNL7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1459832 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726202

African (AFR) AF: 0.0000896 AC: 3 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51934

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111700

Other (OTH) AF: 0.00 AC: 0 AN: 60328

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	12
DANN	Benign	0.82
DEOGEN2	Benign	0.030	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.46
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.019
Sift	Benign	0.86	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.41		Gain of methylation at W44 (P = 0.0197)
MVP		0.088
MPC		0.15
ClinPred		0.060	T
GERP RS		-5.2
PromoterAI		0.072	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.074
gMVP		0.12
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.36		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.36		Position offset: -4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1037468456; hg19: chr15-59063724;