Genetic Variant MINDY2:p.Ser72Phe (chr15-58771610-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001040450.3(MINDY2):c.215C>T(p.Ser72Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,611,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

MINDY2
NM_001040450.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.252

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06798139).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MINDY2	NM_001040450.3 link	c.215C>T	p.Ser72Phe	missense_variant	Exon 1 of 9	ENST00000559228.6	NP_001035540.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MINDY2	ENST00000559228.6 link	c.215C>T	p.Ser72Phe	missense_variant	Exon 1 of 9	2	NM_001040450.3	ENSP00000452885.1	Q8NBR6-1
MINDY2	ENST00000450403.3 link	c.215C>T	p.Ser72Phe	missense_variant	Exon 1 of 9	1		ENSP00000393231.2	Q8NBR6-2
MINDY2	ENST00000316848.9 link	n.215C>T		non_coding_transcript_exon_variant	Exon 1 of 8	1		ENSP00000326194.5	J3KNL7
MINDY2	ENST00000560289.5 link	n.215C>T		non_coding_transcript_exon_variant	Exon 1 of 9	1		ENSP00000453425.1	H0YM15

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1459798

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726144

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

T;.

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.068

T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.67

N;N

REVEL

Benign

0.044

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.030

D;D

Polyphen

0.0

B;B

Vest4

0.12

MutPred

0.27

Gain of catalytic residue at S72 (P = 8e-04);Gain of catalytic residue at S72 (P = 8e-04);

MVP

0.25

MPC

0.11

ClinPred

0.14

GERP RS

2.7

Varity_R

0.056

gMVP

0.21

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over