Variant chr15-58771946-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001040450.3(MINDY2):c.551C>A(p.Ser184Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000057 in 1,403,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

MINDY2
NM_001040450.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.71

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33430806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MINDY2	NM_001040450.3 linkuse as main transcript	c.551C>A	p.Ser184Tyr	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.551C>A	p.Ser184Tyr	missense_variant	1/9	2	NM_001040450.3	ENSP00000452885.1	Q8NBR6-1
MINDY2	ENST00000450403.3 linkuse as main transcript	c.551C>A	p.Ser184Tyr	missense_variant	1/9	1		ENSP00000393231.2	Q8NBR6-2
MINDY2	ENST00000316848.9 linkuse as main transcript	n.551C>A		non_coding_transcript_exon_variant	1/8	1		ENSP00000326194.5	J3KNL7
MINDY2	ENST00000560289.5 linkuse as main transcript	n.551C>A		non_coding_transcript_exon_variant	1/9	1		ENSP00000453425.1	H0YM15

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000570

AC:

AN:

1403724

Hom.:

Cov.:

AF XY:

0.00000578

AC XY:

AN XY:

692588

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:

0.00000737

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Jan 10, 2022

The c.551C>A (p.S184Y) alteration is located in exon 1 (coding exon 1) of the FAM63B gene. This alteration results from a C to A substitution at nucleotide position 551, causing the serine (S) at amino acid position 184 to be replaced by a tyrosine (Y). 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

Uncertain

0.49

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.073

T;.

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.058

MetaRNN

Benign

0.33

T;T

MetaSVM

Benign

-0.67

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.20

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.015

D;D

Polyphen

1.0

D;D

Vest4

0.61

MutPred

0.24

Gain of catalytic residue at S184 (P = 0.0135);Gain of catalytic residue at S184 (P = 0.0135);

MVP

0.75

MPC

0.52

ClinPred

0.96

GERP RS

3.9

Varity_R

0.79

gMVP

0.53

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.

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