12-122208118-TA-TAA

Variant names:

• chr12-122208118-T-TA
• rs138260989
• NM_030765.4:c.*738dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_030765.4(B3GNT4):​c.*738dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0604 in 658,770 control chromosomes in the GnomAD database, including 1,460 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.055 (320 hom., cov: 32)
  • Exomes 𝑓: 0.062 (1140 hom.)
• Consequence: B3GNT4 NM_030765.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.238
• Publications: 1 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

  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

ENSG00000256861 (HGNC:):

ACMG classification

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

• BP6: Variant 12-122208118-T-TA is Benign according to our data. Variant chr12-122208118-T-TA is described in ClinVar as Benign. ClinVar VariationId is 1279245.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0822 is higher than 0.05.

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.*738dupA		3_prime_UTR	Exon 3 of 3	NP_110392.1	Q9C0J1-1
	DIABLO	NM_001371333.1	MANE Select	c.*262dupT		3_prime_UTR	Exon 6 of 6	NP_001358262.1	A0A0S2Z5U7
	B3GNT4	NM_001330492.2		c.*738dupA		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.*738dupA		3_prime_UTR	Exon 3 of 3	ENSP00000319636.4	Q9C0J1-1
	DIABLO	ENST00000464942.7	TSL:1 MANE Select	c.*262dupT		3_prime_UTR	Exon 6 of 6	ENSP00000442360.2	Q9NR28-1
	DIABLO	ENST00000267169.11	TSL:1	c.*438dupT		3_prime_UTR	Exon 7 of 7	ENSP00000267169.7	A0A2U3TZH2

Frequencies

GnomAD3 genomes AF: 0.0546 AC: 8286 AN: 151770 Hom.: 320 Cov.: 32

Gnomad AFR AF: 0.0202

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0351

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.0231

Gnomad FIN AF: 0.0642

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0840

Gnomad OTH AF: 0.0544

GnomAD2 exomes AF: 0.0512 AC: 6694 AN: 130736 AF XY: 0.0518

Gnomad AFR exome AF: 0.0188

Gnomad AMR exome AF: 0.0273

Gnomad ASJ exome AF: 0.0576

Gnomad EAS exome AF: 0.000286

Gnomad FIN exome AF: 0.0698

Gnomad NFE exome AF: 0.0836

Gnomad OTH exome AF: 0.0604

GnomAD4 exome AF: 0.0621 AC: 31476 AN: 506882 Hom.: 1140 Cov.: 4 AF XY: 0.0614 AC XY: 16913 AN XY: 275420

African (AFR) AF: 0.0202 AC: 300 AN: 14884

American (AMR) AF: 0.0275 AC: 917 AN: 33356

Ashkenazi Jewish (ASJ) AF: 0.0552 AC: 1038 AN: 18812

East Asian (EAS) AF: 0.000427 AC: 12 AN: 28128

South Asian (SAS) AF: 0.0283 AC: 1743 AN: 61490

European-Finnish (FIN) AF: 0.0632 AC: 1848 AN: 29230

Middle Eastern (MID) AF: 0.0789 AC: 179 AN: 2270

European-Non Finnish (NFE) AF: 0.0822 AC: 23890 AN: 290714

Other (OTH) AF: 0.0553 AC: 1549 AN: 27998

GnomAD4 genome AF: 0.0545 AC: 8283 AN: 151888 Hom.: 320 Cov.: 32 AF XY: 0.0524 AC XY: 3892 AN XY: 74236

African (AFR) AF: 0.0201 AC: 834 AN: 41428

American (AMR) AF: 0.0350 AC: 535 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0536 AC: 186 AN: 3468

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5146

South Asian (SAS) AF: 0.0233 AC: 112 AN: 4806

European-Finnish (FIN) AF: 0.0642 AC: 677 AN: 10542

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0840 AC: 5706 AN: 67918

Other (OTH) AF: 0.0538 AC: 113 AN: 2100

Alfa AF: 0.0471 Hom.: 63

Bravo AF: 0.0505

Asia WGS AF: 0.0180 AC: 63 AN: 3476

ClinVar

ClinVar submissions

Significance: 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
PhyloP100		-0.24
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: rs138260989; hg19: chr12-122692665;