Genetic Variant NM_001040450.3:c.551C>A (chr15-58771946-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001040450.3(MINDY2):c.551C>A(p.Ser184Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000057 in 1,403,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

MINDY2
NM_001040450.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.71

Publications

0 publications found

Variant links:

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 links:

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

MINDY2-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33430806).

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.551C>A	p.Ser184Tyr	missense	Exon 1 of 9	NP_001035540.1	Q8NBR6-1
	MINDY2	NM_001040453.3		c.551C>A	p.Ser184Tyr	missense	Exon 1 of 9	NP_001035543.1	Q8NBR6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MINDY2	ENST00000559228.6	TSL:2 MANE Select	c.551C>A	p.Ser184Tyr	missense	Exon 1 of 9	ENSP00000452885.1	Q8NBR6-1
MINDY2	ENST00000450403.3	TSL:1	c.551C>A	p.Ser184Tyr	missense	Exon 1 of 9	ENSP00000393231.2	Q8NBR6-2
MINDY2	ENST00000316848.9	TSL:1	n.551C>A		non_coding_transcript_exon	Exon 1 of 8	ENSP00000326194.5	J3KNL7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

200304

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000570

AC:

AN:

1403724

Hom.:

Cov.:

AF XY:

0.00000578

AC XY:

AN XY:

692588

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31628

American (AMR)

AF:

0.00

AC:

AN:

35696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21804

East Asian (EAS)

AF:

0.00

AC:

AN:

39226

South Asian (SAS)

AF:

0.00

AC:

AN:

76296

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51026

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5464

European-Non Finnish (NFE)

AF:

0.00000737

AC:

AN:

1084780

Other (OTH)

AF:

0.00

AC:

AN:

57804

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.073

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.058

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.67

PhyloP100

5.7

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.9

REVEL

Benign

0.20

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.015

Polyphen

1.0

Vest4

0.61

MutPred

0.24

Gain of catalytic residue at S184 (P = 0.0135)

MVP

0.75

MPC

0.52

ClinPred

0.96

GERP RS

3.9

Varity_R

0.79

gMVP

0.53

Mutation Taster

=60/40

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over