rs559000145

Variant names:

• chr12-122208303-C-T
• rs559000145
• NM_030765.4:c.*915C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_030765.4(B3GNT4):​c.*915C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,546,770 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00088 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (2 hom.)
• Consequence: B3GNT4 NM_030765.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.01
• Publications: 0 publications found

Genes affected

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]

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 64

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ENSG00000256861 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 12-122208303-C-T is Benign according to our data. Variant chr12-122208303-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1327665.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030765.4. 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
	B3GNT4	NM_030765.4	MANE Select	c.*915C>T		3_prime_UTR	Exon 3 of 3	NP_110392.1	Q9C0J1-1
	DIABLO	NM_001371333.1	MANE Select	c.*78G>A		3_prime_UTR	Exon 6 of 6	NP_001358262.1	A0A0S2Z5U7
	B3GNT4	NM_001330492.2		c.*915C>T		3_prime_UTR	Exon 2 of 2	NP_001317421.1	Q9C0J1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B3GNT4	ENST00000324189.5	TSL:1 MANE Select	c.*915C>T		3_prime_UTR	Exon 3 of 3	ENSP00000319636.4	Q9C0J1-1
	DIABLO	ENST00000464942.7	TSL:1 MANE Select	c.*78G>A		3_prime_UTR	Exon 6 of 6	ENSP00000442360.2	Q9NR28-1
	DIABLO	ENST00000267169.11	TSL:1	c.*254G>A		3_prime_UTR	Exon 7 of 7	ENSP00000267169.7	A0A2U3TZH2

Frequencies

GnomAD3 genomes AF: 0.000880 AC: 134 AN: 152218 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000506

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00157

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000884 AC: 211 AN: 238604 AF XY: 0.000839

Gnomad AFR exome AF: 0.000705

Gnomad AMR exome AF: 0.000350

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000308

Gnomad NFE exome AF: 0.00165

Gnomad OTH exome AF: 0.000675

GnomAD4 exome AF: 0.00119 AC: 1653 AN: 1394434 Hom.: 2 Cov.: 25 AF XY: 0.00112 AC XY: 778 AN XY: 697012

African (AFR) AF: 0.000310 AC: 10 AN: 32212

American (AMR) AF: 0.000359 AC: 16 AN: 44516

Ashkenazi Jewish (ASJ) AF: 0.0000388 AC: 1 AN: 25774

East Asian (EAS) AF: 0.00 AC: 0 AN: 39436

South Asian (SAS) AF: 0.00 AC: 0 AN: 84814

European-Finnish (FIN) AF: 0.000411 AC: 18 AN: 43806

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4030

European-Non Finnish (NFE) AF: 0.00144 AC: 1533 AN: 1061516

Other (OTH) AF: 0.00129 AC: 75 AN: 58330

GnomAD4 genome AF: 0.000880 AC: 134 AN: 152336 Hom.: 0 Cov.: 33 AF XY: 0.000725 AC XY: 54 AN XY: 74490

African (AFR) AF: 0.000505 AC: 21 AN: 41592

American (AMR) AF: 0.000327 AC: 5 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00157 AC: 107 AN: 68022

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00100 Hom.: 0

Bravo AF: 0.000842

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.13
DANN	Benign	0.46
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism

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: rs559000145; hg19: chr12-122692850;