Variant 15-58771706-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001040450.3(MINDY2):c.311G>A(p.Gly104Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000558 in 1,612,330 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00054 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00056 ( 2 hom. )

Consequence

MINDY2
NM_001040450.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.597

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013770103).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MINDY2	NM_001040450.3 linkuse as main transcript	c.311G>A	p.Gly104Glu	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.311G>A	p.Gly104Glu	missense_variant	1/9	2	NM_001040450.3	ENSP00000452885.1	Q8NBR6-1
MINDY2	ENST00000450403.3 linkuse as main transcript	c.311G>A	p.Gly104Glu	missense_variant	1/9	1		ENSP00000393231.2	Q8NBR6-2
MINDY2	ENST00000316848.9 linkuse as main transcript	n.311G>A		non_coding_transcript_exon_variant	1/8	1		ENSP00000326194.5	J3KNL7
MINDY2	ENST00000560289.5 linkuse as main transcript	n.311G>A		non_coding_transcript_exon_variant	1/9	1		ENSP00000453425.1	H0YM15

Frequencies

GnomAD3 genomes

AF:

0.000539

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000808

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000733

AC:

177

AN:

241616

Hom.:

AF XY:

0.000852

AC XY:

113

AN XY:

132608

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000933

Gnomad ASJ exome

AF:

0.00152

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000786

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000929

Gnomad OTH exome

AF:

0.00102

GnomAD4 exome

AF:

0.000560

AC:

817

AN:

1460000

Hom.:

Cov.:

AF XY:

0.000607

AC XY:

441

AN XY:

726338

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000851

Gnomad4 ASJ exome

AF:

0.00176

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000777

Gnomad4 FIN exome

AF:

0.0000768

Gnomad4 NFE exome

AF:

0.000509

Gnomad4 OTH exome

AF:

0.000879

GnomAD4 genome

AF:

0.000538

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000808

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000831

Hom.:

Bravo

AF:

0.000623

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00130

AC:

ExAC

AF:

0.000736

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00125

EpiControl

AF:

0.00166

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

Sep 16, 2021

The c.311G>A (p.G104E) 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 311, causing the glycine (G) at amino acid position 104 to be replaced by a glutamic acid (E). 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

0.098

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.037

T;.

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.96

N;N

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.55

N;N

REVEL

Benign

0.025

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.16

T;T

Polyphen

0.0010

B;B

Vest4

0.21

MVP

0.45

MPC

0.53

ClinPred

0.15

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.40

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over