15-58771877-G-T

Variant names:

• chr15-58771877-G-T
• NM_001040450.3:c.482G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040450.3(MINDY2):​c.482G>T​(p.Cys161Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000702 in 1,424,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. C161Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: MINDY2 NM_001040450.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.32

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1272786).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MINDY2	NM_001040450.3	c.482G>T	p.Cys161Phe	missense_variant	Exon 1 of 9	ENST00000559228.6	NP_001035540.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MINDY2	ENST00000559228.6	c.482G>T	p.Cys161Phe	missense_variant	Exon 1 of 9	2	NM_001040450.3	ENSP00000452885.1
MINDY2	ENST00000450403.3	c.482G>T	p.Cys161Phe	missense_variant	Exon 1 of 9	1		ENSP00000393231.2
MINDY2	ENST00000316848.9	n.482G>T		non_coding_transcript_exon_variant	Exon 1 of 8	1		ENSP00000326194.5
MINDY2	ENST00000560289.5	n.482G>T		non_coding_transcript_exon_variant	Exon 1 of 9	1		ENSP00000453425.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1424292 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 705550

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: 9.13e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.029	T;.
Eigen	Benign	0.012
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.95	T
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.61	N;N
REVEL	Benign	0.044
Sift	Uncertain	0.028	D;D
Sift4G	Benign	0.29	T;T
Polyphen		0.29	B;B
Vest4		0.19
MutPred		0.14		Gain of glycosylation at S162 (P = 0.0453);Gain of glycosylation at S162 (P = 0.0453);
MVP		0.51
MPC		0.24
ClinPred		0.79	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.57
gMVP		0.088

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: chr15-59064076;