Genetic Variant DIABLO:p.Gly224Trp (chr12-122208431-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001371333.1(DIABLO):c.670G>T(p.Gly224Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G224R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

DIABLO
NM_001371333.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.462

Publications

0 publications found

Variant links:

Genes affected

DIABLO (HGNC:21528): (diablo IAP-binding mitochondrial protein) This gene encodes an inhibitor of apoptosis protein (IAP)-binding protein. The encoded mitochondrial protein enters the cytosol when cells undergo apoptosis, and allows activation of caspases by binding to inhibitor of apoptosis proteins. Overexpression of the encoded protein sensitizes tumor cells to apoptosis. A mutation in this gene is associated with young-adult onset of nonsyndromic deafness-64. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]

DIABLO links:

B3GNT4 (HGNC:15683): (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 4) This gene encodes a member of the beta-1,3-N-acetylglucosaminyltransferase protein family. The encoded enzyme is involved in the biosynthesis of poly-N-acetyllactosamine chains and prefers lacto-N-neotetraose as a substrate. It is a type II transmembrane protein. [provided by RefSeq, Jul 2008]

B3GNT4 links:

ENSG00000256861 (HGNC:):

ENSG00000256861 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24269894).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371333.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DIABLO	NM_001371333.1	MANE Select	c.670G>T	p.Gly224Trp	missense	Exon 6 of 6	NP_001358262.1	A0A0S2Z5U7
B3GNT4	NM_030765.4	MANE Select	c.*1043C>A		3_prime_UTR	Exon 3 of 3	NP_110392.1	Q9C0J1-1
DIABLO	NM_019887.6		c.670G>T	p.Gly224Trp	missense	Exon 7 of 7	NP_063940.1	A0A0S2Z5U7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DIABLO	ENST00000464942.7	TSL:1 MANE Select	c.670G>T	p.Gly224Trp	missense	Exon 6 of 6	ENSP00000442360.2	Q9NR28-1
DIABLO	ENST00000353548.11	TSL:1	c.538G>T	p.Gly180Trp	missense	Exon 5 of 5	ENSP00000320343.6	Q9NR28-3
B3GNT4	ENST00000324189.5	TSL:1 MANE Select	c.*1043C>A		3_prime_UTR	Exon 3 of 3	ENSP00000319636.4	Q9C0J1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.022

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.45

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.84

M_CAP

Benign

0.068

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.1

PhyloP100

0.46

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.39

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.020

Polyphen

0.99

Vest4

0.35

MutPred

0.47

Gain of helix (P = 0.0496)

MVP

0.80

MPC

0.20

ClinPred

0.64

GERP RS

0.19

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.17

gMVP

0.13

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over