Variant 15-58771840-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001040450.3(MINDY2):c.445G>A(p.Glu149Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,454,300 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: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MINDY2
NM_001040450.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.420

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 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=0.08360553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MINDY2	NM_001040450.3 linkuse as main transcript	c.445G>A	p.Glu149Lys	missense_variant	1/9	ENST00000559228.6	NP_001035540.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MINDY2	ENST00000559228.6 linkuse as main transcript	c.445G>A	p.Glu149Lys	missense_variant	1/9	2	NM_001040450.3	ENSP00000452885.1	Q8NBR6-1
MINDY2	ENST00000450403.3 linkuse as main transcript	c.445G>A	p.Glu149Lys	missense_variant	1/9	1		ENSP00000393231.2	Q8NBR6-2
MINDY2	ENST00000316848.9 linkuse as main transcript	n.445G>A		non_coding_transcript_exon_variant	1/8	1		ENSP00000326194.5	J3KNL7
MINDY2	ENST00000560289.5 linkuse as main transcript	n.445G>A		non_coding_transcript_exon_variant	1/9	1		ENSP00000453425.1	H0YM15

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1454300

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723028

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:

0.00000271

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2024

The c.445G>A (p.E149K) alteration is located in exon 1 (coding exon 1) of the FAM63B gene. This alteration results from a G to A substitution at nucleotide position 445, causing the glutamic acid (E) at amino acid position 149 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

T;.

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.084

T;T

MetaSVM

Benign

-1.0

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.52

N;N

REVEL

Benign

0.039

Sift

Uncertain

0.0080

D;D

Sift4G

Benign

0.43

T;T

Polyphen

0.043

B;B

Vest4

0.10

MutPred

0.19

Gain of ubiquitination at E149 (P = 0.0045);Gain of ubiquitination at E149 (P = 0.0045);

MVP

0.36

MPC

0.094

ClinPred

0.24

GERP RS

3.0

Varity_R

0.11

gMVP

0.18

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over