Genetic Variant DIABLO:c.-11C>A (chr12-122226025-G-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001371333.1(DIABLO):c.-11C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000621 in 1,448,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

DIABLO
NM_001371333.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.712

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 Gene-Disease associations (from GenCC):

autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal dominant nonsyndromic hearing loss 64
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
nonsyndromic genetic hearing loss
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

DIABLO links:

ENSG00000256861 (HGNC:):

ENSG00000256861 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BS2

High AC in GnomAdExome4 at 9 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	Effect	Exon Rank	Protein	UniProt
DIABLO	NM_001371333.1	MANE Select	c.-11C>A	5_prime_UTR	Exon 1 of 6	NP_001358262.1	A0A0S2Z5U7
DIABLO	NM_019887.6		c.-11C>A	5_prime_UTR	Exon 2 of 7	NP_063940.1	A0A0S2Z5U7
DIABLO	NM_001278342.1		c.-11C>A	5_prime_UTR	Exon 1 of 5	NP_001265271.1	Q9NR28-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DIABLO	ENST00000464942.7	TSL:1 MANE Select	c.-11C>A	5_prime_UTR	Exon 1 of 6	ENSP00000442360.2	Q9NR28-1
DIABLO	ENST00000267169.11	TSL:1	c.-11C>A	5_prime_UTR	Exon 1 of 7	ENSP00000267169.7	A0A2U3TZH2
DIABLO	ENST00000353548.11	TSL:1	c.-11C>A	5_prime_UTR	Exon 1 of 5	ENSP00000320343.6	Q9NR28-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000621

AC:

AN:

1448966

Hom.:

Cov.:

AF XY:

0.00000555

AC XY:

AN XY:

720086

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33250

American (AMR)

AF:

0.00

AC:

AN:

43428

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25818

East Asian (EAS)

AF:

0.00

AC:

AN:

39310

South Asian (SAS)

AF:

0.00

AC:

AN:

84724

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50214

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5068

European-Non Finnish (NFE)

AF:

0.00000813

AC:

AN:

1107272

Other (OTH)

AF:

0.00

AC:

AN:

59882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.403

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

1.9

(source)

DANN

Benign

0.65

PhyloP100

-0.71

PromoterAI

0.0055

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over