Genetic Variant MINDY3:p.Asp325Asn (chr10-15789302-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024948.4(MINDY3):c.973G>A(p.Asp325Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000584 in 1,610,530 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000048 ( 1 hom. )

Consequence

MINDY3
NM_024948.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.36

Variant links:

Genes affected

MINDY3 (HGNC:23578): (MINDY lysine 48 deubiquitinase 3) The protein encoded by this gene contains a caspase-associated recruitment domain and may function in apoptosis. It has been identified as a tumor suppressor in lung and gastric cancers, and a polymorphism in the gene may be associated with gastric cancer risk. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2015]

MINDY3 links:

LOC124902383 (HGNC:):

LOC124902383 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.118732035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MINDY3	NM_024948.4 link	c.973G>A	p.Asp325Asn	missense_variant	Exon 12 of 15	ENST00000277632.8	NP_079224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MINDY3	ENST00000277632.8 link	c.973G>A	p.Asp325Asn	missense_variant	Exon 12 of 15	1	NM_024948.4	ENSP00000277632.3	Q9H8M7-1
MINDY3	ENST00000477891.1 link	n.1120G>A		non_coding_transcript_exon_variant	Exon 11 of 14	1
MINDY3	ENST00000418767.5 link	c.493G>A	p.Asp165Asn	missense_variant	Exon 7 of 7	3		ENSP00000388661.1	X6RC30
MINDY3	ENST00000378036.5 link	c.88G>A	p.Asp30Asn	missense_variant	Exon 3 of 6	2		ENSP00000367275.1	X6R9S5

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

151802

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00125

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000124

AC:

AN:

249972

Hom.:

AF XY:

0.000126

AC XY:

AN XY:

135158

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000726

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000480

AC:

AN:

1458728

Hom.:

Cov.:

AF XY:

0.0000496

AC XY:

AN XY:

725738

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000560

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.0000581

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000315

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000158

AC:

AN:

151802

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74104

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00125

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000566

Hom.:

Bravo

AF:

0.000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000548

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.973G>A (p.D325N) alteration is located in exon 12 (coding exon 12) of the FAM188A gene. This alteration results from a G to A substitution at nucleotide position 973, causing the aspartic acid (D) at amino acid position 325 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

0.14

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.029

.;T;.

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.69

PROVEAN

Benign

0.35

N;N;N

REVEL

Benign

0.086

Sift

Benign

0.24

T;T;T

Sift4G

Benign

0.55

T;T;T

Polyphen

0.80

.;P;.

Vest4

0.60

MVP

0.13

MPC

0.13

ClinPred

0.10

GERP RS

5.2

Varity_R

0.084

gMVP

0.58

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