rs35426428

Variant names:

• chr12-122208411-C-T
• rs35426428
• NM_001371333.1:c.690G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001371333.1(DIABLO):​c.690G>A​(p.Ser230Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0177 in 1,613,036 control chromosomes in the GnomAD database, including 3,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.089 (1974 hom., cov: 32)
  • Exomes 𝑓: 0.010 (1814 hom.)
• Consequence: DIABLO NM_001371333.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -2.45
• Publications: 6 publications found

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]

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]

ENSG00000256861 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 12-122208411-C-T is Benign according to our data. Variant chr12-122208411-C-T is described in ClinVar as Benign. ClinVar VariationId is 226562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.45 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIABLO	NM_001371333.1	MANE Select	c.690G>A	p.Ser230Ser	synonymous	Exon 6 of 6	NP_001358262.1	A0A0S2Z5U7
	B3GNT4	NM_030765.4	MANE Select	c.*1023C>T		3_prime_UTR	Exon 3 of 3	NP_110392.1	Q9C0J1-1
	DIABLO	NM_019887.6		c.690G>A	p.Ser230Ser	synonymous	Exon 7 of 7	NP_063940.1	A0A0S2Z5U7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIABLO	ENST00000464942.7	TSL:1 MANE Select	c.690G>A	p.Ser230Ser	synonymous	Exon 6 of 6	ENSP00000442360.2	Q9NR28-1
	DIABLO	ENST00000353548.11	TSL:1	c.558G>A	p.Ser186Ser	synonymous	Exon 5 of 5	ENSP00000320343.6	Q9NR28-3
	B3GNT4	ENST00000324189.5	TSL:1 MANE Select	c.*1023C>T		3_prime_UTR	Exon 3 of 3	ENSP00000319636.4	Q9C0J1-1

Frequencies

GnomAD3 genomes AF: 0.0891 AC: 13550 AN: 152112 Hom.: 1969 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0353

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00141

Gnomad OTH AF: 0.0583

GnomAD2 exomes AF: 0.0247 AC: 6148 AN: 249380 AF XY: 0.0185

Gnomad AFR exome AF: 0.313

Gnomad AMR exome AF: 0.0167

Gnomad ASJ exome AF: 0.0259

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00143

Gnomad OTH exome AF: 0.0123

GnomAD4 exome AF: 0.0103 AC: 15000 AN: 1460806 Hom.: 1814 Cov.: 31 AF XY: 0.00901 AC XY: 6550 AN XY: 726642

African (AFR) AF: 0.328 AC: 10966 AN: 33450

American (AMR) AF: 0.0181 AC: 811 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0287 AC: 749 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00128 AC: 110 AN: 86072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53142

Middle Eastern (MID) AF: 0.0165 AC: 87 AN: 5262

European-Non Finnish (NFE) AF: 0.000789 AC: 877 AN: 1112002

Other (OTH) AF: 0.0232 AC: 1398 AN: 60318

GnomAD4 genome AF: 0.0892 AC: 13583 AN: 152230 Hom.: 1974 Cov.: 32 AF XY: 0.0865 AC XY: 6435 AN XY: 74436

African (AFR) AF: 0.306 AC: 12712 AN: 41492

American (AMR) AF: 0.0353 AC: 540 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0291 AC: 101 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00141 AC: 96 AN: 68010

Other (OTH) AF: 0.0577 AC: 122 AN: 2114

Alfa AF: 0.0397 Hom.: 532

Bravo AF: 0.103

EpiCase AF: 0.00207

EpiControl AF: 0.00172

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.5
DANN	Benign	0.60
PhyloP100		-2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35426428; hg19: chr12-122692958;