rs587724501

Variant summary

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

The NM_001376665.1(MINDY1):​c.1360G>C​(p.Gly454Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

MINDY1
NM_001376665.1 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0430
Variant links:
Genes affected
MINDY1 (HGNC:25648): (MINDY lysine 48 deubiquitinase 1) Enables K48-linked polyubiquitin modification-dependent protein binding activity; Lys48-specific deubiquitinase activity; and cysteine-type carboxypeptidase activity. Predicted to be involved in protein K48-linked deubiquitination. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.060963035).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MINDY1NM_001376665.1 linkc.1360G>C p.Gly454Arg missense_variant Exon 10 of 10 ENST00000683666.2 NP_001363594.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MINDY1ENST00000683666.2 linkc.1360G>C p.Gly454Arg missense_variant Exon 10 of 10 NM_001376665.1 ENSP00000507359.1 Q8N5J2-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.90e-7
AC:
1
AN:
1449792
Hom.:
0
Cov.:
31
AF XY:
0.00000139
AC XY:
1
AN XY:
720160
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:
0.0000119
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
7.1
DANN
Benign
0.81
DEOGEN2
Benign
0.0048
T;.;T;.;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.090
N
LIST_S2
Benign
0.72
T;T;.;T;T
M_CAP
Benign
0.0045
T
MetaRNN
Benign
0.061
T;T;T;T;T
MetaSVM
Benign
-0.97
T
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.41
.;N;N;N;N
REVEL
Benign
0.0060
Sift
Benign
0.079
.;T;T;T;T
Sift4G
Uncertain
0.012
D;T;D;D;T
Polyphen
0.20
B;.;B;B;.
Vest4
0.10
MutPred
0.18
Gain of helix (P = 0.0117);.;Gain of helix (P = 0.0117);.;.;
MVP
0.21
MPC
0.30
ClinPred
0.27
T
GERP RS
0.92
Varity_R
0.042
gMVP
0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-150969813; API