NM_006006.6:c.283A>C

Variant names:

• chr11-114063583-A-C
• NM_006006.6:c.283A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006006.6(ZBTB16):​c.283A>C​(p.Lys95Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZBTB16 NM_006006.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.19
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31224328).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB16	NM_006006.6	MANE Select	c.283A>C	p.Lys95Gln	missense	Exon 2 of 7	NP_005997.2
	ZBTB16	NM_001018011.3		c.283A>C	p.Lys95Gln	missense	Exon 2 of 7	NP_001018011.1	A0A024R3C6
	ZBTB16	NM_001354750.2		c.283A>C	p.Lys95Gln	missense	Exon 2 of 7	NP_001341679.1	Q05516-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB16	ENST00000335953.9	TSL:1 MANE Select	c.283A>C	p.Lys95Gln	missense	Exon 2 of 7	ENSP00000338157.4	Q05516-1
	ZBTB16	ENST00000392996.2	TSL:1	c.283A>C	p.Lys95Gln	missense	Exon 2 of 7	ENSP00000376721.2	Q05516-1
	ZBTB16	ENST00000541602.5	TSL:1	n.531A>C		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.51	N
PhyloP100		7.2
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.23
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.92	P
Vest4		0.63
MutPred		0.35		Loss of ubiquitination at K95 (P = 0.0141)
MVP		0.46
MPC		0.63
ClinPred		0.88	D
GERP RS		5.5
Varity_R		0.82
gMVP		0.60
Mutation Taster		=76/24	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

hg19: chr11-113934305;