15-58771610-C-T

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

4
14

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]

Genome browser will be placed here

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
MINDY2NM_001040450.3 linkc.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 Appris UniProt
MINDY2ENST00000559228.6 linkc.215C>T p.Ser72Phe missense_variant Exon 1 of 9 2 NM_001040450.3 ENSP00000452885.1 Q8NBR6-1
MINDY2ENST00000450403.3 linkc.215C>T p.Ser72Phe missense_variant Exon 1 of 9 1 ENSP00000393231.2 Q8NBR6-2
MINDY2ENST00000316848.9 linkn.215C>T non_coding_transcript_exon_variant Exon 1 of 8 1 ENSP00000326194.5 J3KNL7
MINDY2ENST00000560289.5 linkn.215C>T non_coding_transcript_exon_variant Exon 1 of 9 1 ENSP00000453425.1 H0YM15

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152160
Hom.:
0
Cov.:
32
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:
7
AN:
1459798
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
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:
1
AN:
152160
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
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
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
12
DANN
Uncertain
1.0
DEOGEN2
Benign
0.025
T;.
Eigen
Benign
-0.82
Eigen_PC
Benign
-0.82
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.66
T;T
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.068
T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Uncertain
0.64
T
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
T
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.

Other links and lift over

dbSNP: rs557342297; hg19: chr15-59063809; API