NM_006006.6:c.1453+3466G>T

Variant names:

• chr11-114190504-G-T
• rs620095
• NM_006006.6:c.1453+3466G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006006.6(ZBTB16):​c.1453+3466G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 151,940 control chromosomes in the GnomAD database, including 5,771 homozygotes. 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: 𝑓 0.25 (5771 hom., cov: 32)
• Consequence: ZBTB16 NM_006006.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629
• Publications: 6 publications found

Genes affected

ZBTB16 (HGNC:12930): (zinc finger and BTB domain containing 16) This gene is a member of the Krueppel C2H2-type zinc-finger protein family and encodes a zinc finger transcription factor that contains nine Kruppel-type zinc finger domains at the carboxyl terminus. This protein is located in the nucleus, is involved in cell cycle progression, and interacts with a histone deacetylase. Specific instances of aberrant gene rearrangement at this locus have been associated with acute promyelocytic leukemia (APL). Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

ZBTB16 Gene-Disease associations (from GenCC):

• skeletal defects, genital hypoplasia, and intellectual disability

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006006.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB16	NM_006006.6	MANE Select	c.1453+3466G>T		intron	N/A	NP_005997.2
	ZBTB16	NM_001018011.3		c.1453+3466G>T		intron	N/A	NP_001018011.1
	ZBTB16	NM_001354750.2		c.1453+3466G>T		intron	N/A	NP_001341679.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB16	ENST00000335953.9	TSL:1 MANE Select	c.1453+3466G>T		intron	N/A	ENSP00000338157.4
	ZBTB16	ENST00000392996.2	TSL:1	c.1453+3466G>T		intron	N/A	ENSP00000376721.2
	ZBTB16	ENST00000865551.1		c.1453+3466G>T		intron	N/A	ENSP00000535610.1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37461 AN: 151820 Hom.: 5746 Cov.: 32

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.247 AC: 37533 AN: 151940 Hom.: 5771 Cov.: 32 AF XY: 0.245 AC XY: 18194 AN XY: 74254

African (AFR) AF: 0.447 AC: 18508 AN: 41396

American (AMR) AF: 0.210 AC: 3211 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 717 AN: 3472

East Asian (EAS) AF: 0.175 AC: 903 AN: 5170

South Asian (SAS) AF: 0.129 AC: 621 AN: 4812

European-Finnish (FIN) AF: 0.162 AC: 1704 AN: 10532

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11016 AN: 67972

Other (OTH) AF: 0.251 AC: 531 AN: 2112

Alfa AF: 0.179 Hom.: 4797

Bravo AF: 0.261

Asia WGS AF: 0.161 AC: 560 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.9
DANN	Benign	0.45
PhyloP100		-0.63
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: rs620095; hg19: chr11-114061226; COSMIC: COSV60098960; COSMIC: COSV60098960;