Variant 1-151000537-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001376665.1(MINDY1):c.655G>A(p.Asp219Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,614,110 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 6 hom. )

Consequence

MINDY1
NM_001376665.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91

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]

MINDY1 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=0.057270885).

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MINDY1	NM_001376665.1 linkuse as main transcript	c.655G>A	p.Asp219Asn	missense_variant	5/10	ENST00000683666.2	NP_001363594.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MINDY1	ENST00000683666.2 linkuse as main transcript	c.655G>A	p.Asp219Asn	missense_variant	5/10		NM_001376665.1	ENSP00000507359	P1	Q8N5J2-1

Frequencies

GnomAD3 genomes

AF:

0.00128

AC:

195

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00250

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000978

AC:

246

AN:

251440

Hom.:

AF XY:

0.000905

AC XY:

123

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00204

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.00137

AC:

2008

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

993

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.000168

Gnomad4 NFE exome

AF:

0.00173

Gnomad4 OTH exome

AF:

0.000894

GnomAD4 genome

AF:

0.00128

AC:

195

AN:

152244

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00250

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00176

Hom.:

Bravo

AF:

0.000986

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.00119

AC:

145

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00169

EpiControl

AF:

0.00160

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

Jun 17, 2024

The c.799G>A (p.D267N) alteration is located in exon 6 (coding exon 5) of the FAM63A gene. This alteration results from a G to A substitution at nucleotide position 799, causing the aspartic acid (D) at amino acid position 267 to be replaced by an asparagine (N). 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

0.16

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.43

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.091

T;.;T;.;.

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.90

D;D;.;D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.057

T;T;T;T;T

MetaSVM

Benign

-0.72

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-2.1

.;N;N;N;N

REVEL

Benign

0.16

Sift

Benign

0.19

.;T;T;D;T

Sift4G

Benign

0.51

T;T;T;T;T

Polyphen

0.99

D;.;D;D;.

Vest4

0.56

MVP

0.69

MPC

0.87

ClinPred

0.14

GERP RS

4.8

Varity_R

0.28

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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