Genetic Variant MINDY3:p.Phe368Leu (chr10-15786575-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024948.4(MINDY3):c.1102T>C(p.Phe368Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MINDY3
NM_024948.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.25

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MINDY3	NM_024948.4 link	c.1102T>C	p.Phe368Leu	missense_variant	Exon 13 of 15	ENST00000277632.8	NP_079224.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MINDY3	ENST00000277632.8 link	c.1102T>C	p.Phe368Leu	missense_variant	Exon 13 of 15	1	NM_024948.4	ENSP00000277632.3	Q9H8M7-1
MINDY3	ENST00000477891.1 link	n.1249T>C		non_coding_transcript_exon_variant	Exon 12 of 14	1
MINDY3	ENST00000378036.5 link	c.217T>C	p.Phe73Leu	missense_variant	Exon 4 of 6	2		ENSP00000367275.1	X6R9S5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1423766

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

710478

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:

0.00

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

May 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1102T>C (p.F368L) alteration is located in exon 13 (coding exon 13) of the FAM188A gene. This alteration results from a T to C substitution at nucleotide position 1102, causing the phenylalanine (F) at amino acid position 368 to be replaced by a leucine (L). 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

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

.;T

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.61

D;D

MetaSVM

Benign

-1.1

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-5.9

D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.0040

D;D

Sift4G

Benign

0.11

T;D

Polyphen

0.057

.;B

Vest4

0.82

MutPred

0.36

.;Gain of disorder (P = 0.1711);

MVP

0.45

MPC

0.42

ClinPred

0.98

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.4

Varity_R

0.76

gMVP

0.73

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