chr12-122208401-CC-AG

Variant names:

• chr12-122208401-CC-AG
• NM_001371333.1:c.699_700delGGinsCT

Variant summary

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

The NM_001371333.1(DIABLO):​c.699_700delGGinsCT​(p.GluAla233AspSer) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DIABLO NM_001371333.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.73
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.699_700delGGinsCT	p.GluAla233AspSer	missense	N/A	NP_001358262.1	A0A0S2Z5U7
	B3GNT4	NM_030765.4	MANE Select	c.*1013_*1014delCCinsAG		3_prime_UTR	Exon 3 of 3	NP_110392.1	Q9C0J1-1
	DIABLO	NM_019887.6		c.699_700delGGinsCT	p.GluAla233AspSer	missense	N/A	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.699_700delGGinsCT	p.GluAla233AspSer	missense	N/A	ENSP00000442360.2	Q9NR28-1
	DIABLO	ENST00000353548.11	TSL:1	c.567_568delGGinsCT	p.GluAla189AspSer	missense	N/A	ENSP00000320343.6	Q9NR28-3
	B3GNT4	ENST00000324189.5	TSL:1 MANE Select	c.*1013_*1014delCCinsAG		3_prime_UTR	Exon 3 of 3	ENSP00000319636.4	Q9C0J1-1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr12-122692948;