rs376530914

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001371333.1(DIABLO):​c.-11C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00023 in 1,601,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

DIABLO
NM_001371333.1 5_prime_UTR

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.712
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 12-122226025-G-A is Benign according to our data. Variant chr12-122226025-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 228567.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BS2
High AC in GnomAd4 at 35 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DIABLONM_001371333.1 linkuse as main transcriptc.-11C>T 5_prime_UTR_variant 1/6 ENST00000464942.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DIABLOENST00000464942.7 linkuse as main transcriptc.-11C>T 5_prime_UTR_variant 1/61 NM_001371333.1 P1Q9NR28-1

Frequencies

GnomAD3 genomes
AF:
0.000230
AC:
35
AN:
152228
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000851
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000265
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000218
AC:
49
AN:
225208
Hom.:
0
AF XY:
0.000235
AC XY:
29
AN XY:
123184
show subpopulations
Gnomad AFR exome
AF:
0.0000737
Gnomad AMR exome
AF:
0.000397
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000117
Gnomad SAS exome
AF:
0.0000349
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000310
Gnomad OTH exome
AF:
0.000177
GnomAD4 exome
AF:
0.000230
AC:
333
AN:
1448964
Hom.:
0
Cov.:
32
AF XY:
0.000211
AC XY:
152
AN XY:
720086
show subpopulations
Gnomad4 AFR exome
AF:
0.0000602
Gnomad4 AMR exome
AF:
0.000322
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000509
Gnomad4 SAS exome
AF:
0.0000354
Gnomad4 FIN exome
AF:
0.0000398
Gnomad4 NFE exome
AF:
0.000266
Gnomad4 OTH exome
AF:
0.000250
GnomAD4 genome
AF:
0.000230
AC:
35
AN:
152346
Hom.:
0
Cov.:
32
AF XY:
0.000201
AC XY:
15
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000850
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000265
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.0000693
Hom.:
0
Bravo
AF:
0.000253

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineAug 18, 2015The c.-11C>T variant in DIABLO has not been previously reported in individuals w ith hearing loss but has been identified in 22/27112 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs376 530914). This variant is in the 5'UTR of DIABLO; however, its effect on transla tion is unknown. In summary the clinical significance of the c.-3G>T variant is uncertain. -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxOct 02, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
CADD
Benign
3.2
DANN
Benign
0.85
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs376530914; hg19: chr12-122710572; API