12-122208431-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001371333.1(DIABLO):c.670G>A(p.Gly224Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000459 in 1,613,946 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

DIABLO
NM_001371333.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.462

Publications

7 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038775206).

BP6

Variant 12-122208431-C-T is Benign according to our data. Variant chr12-122208431-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 288171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 380 AD gene.

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>A	p.Gly224Arg	missense	Exon 6 of 6	NP_001358262.1	A0A0S2Z5U7
B3GNT4	NM_030765.4	MANE Select	c.*1043C>T		3_prime_UTR	Exon 3 of 3	NP_110392.1	Q9C0J1-1
DIABLO	NM_019887.6		c.670G>A	p.Gly224Arg	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>A	p.Gly224Arg	missense	Exon 6 of 6	ENSP00000442360.2	Q9NR28-1
DIABLO	ENST00000353548.11	TSL:1	c.538G>A	p.Gly180Arg	missense	Exon 5 of 5	ENSP00000320343.6	Q9NR28-3
B3GNT4	ENST00000324189.5	TSL:1 MANE Select	c.*1043C>T		3_prime_UTR	Exon 3 of 3	ENSP00000319636.4	Q9C0J1-1

Frequencies

GnomAD3 genomes

AF:

0.00250

AC:

380

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00863

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000608

AC:

152

AN:

250108

AF XY:

0.000421

show subpopulations

Gnomad AFR exome

AF:

0.00772

Gnomad AMR exome

AF:

0.000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000622

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000247

AC:

361

AN:

1461584

Hom.:

Cov.:

AF XY:

0.000223

AC XY:

162

AN XY:

727066

show subpopulations

African (AFR)

AF:

0.00792

AC:

265

AN:

33470

American (AMR)

AF:

0.000626

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53262

Middle Eastern (MID)

AF:

0.000177

AC:

AN:

5662

European-Non Finnish (NFE)

AF:

0.0000324

AC:

AN:

1112010

Other (OTH)

AF:

0.000513

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00249

AC:

380

AN:

152362

Hom.:

Cov.:

AF XY:

0.00236

AC XY:

176

AN XY:

74514

show subpopulations

African (AFR)

AF:

0.00861

AC:

358

AN:

41586

American (AMR)

AF:

0.00105

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68038

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.00283

ESP6500AA

AF:

0.00658

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000741

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

DIABLO-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.25

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.78

M_CAP

Benign

0.023

MetaRNN

Benign

0.0039

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.20

PhyloP100

0.46

PrimateAI

Benign

0.30

PROVEAN

Benign

0.59

REVEL

Benign

0.092

Sift

Benign

0.15

Sift4G

Benign

0.41

Polyphen

0.0050

Vest4

0.11

MutPred

0.47

Gain of helix (P = 0.0496)

MVP

0.71

MPC

0.036

ClinPred

0.0067

GERP RS

0.19

Varity_R

0.068

gMVP

0.087

Mutation Taster

=92/8

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over