11-114250382-A-G

Position:

• chr11-114250382-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP2 PP3

The NM_006006.6(ZBTB16):​c.1849A>G​(p.Met617Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZBTB16 NM_006006.6 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 9.25

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ZBTB16. . Gene score misZ 2.4714 (greater than the threshold 3.09). Trascript score misZ 3.8406 (greater than threshold 3.09). GenCC has associacion of gene with skeletal defects, genital hypoplasia, and intellectual disability.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.837

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB16	NM_006006.6	c.1849A>G	p.Met617Val	missense_variant	7/7	ENST00000335953.9	NP_005997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB16	ENST00000335953.9	c.1849A>G	p.Met617Val	missense_variant	7/7	1	NM_006006.6	ENSP00000338157.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Skeletal defects, genital hypoplasia, and intellectual disability Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Nov 01, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.80	.;T
M_CAP	Benign	0.054	D
MetaRNN	Pathogenic	0.84	D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	0.76	N;N
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.4	N;N
REVEL	Uncertain	0.48
Sift	Uncertain	0.018	D;D
Sift4G	Uncertain	0.017	D;D
Polyphen		0.96	D;D
Vest4		0.92
MutPred		0.62		Loss of disorder (P = 0.0924);Loss of disorder (P = 0.0924);
MVP		0.92
MPC		2.4
ClinPred		0.95	D
GERP RS		5.3
Varity_R		0.51
gMVP		0.91

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

Publications

LitVar

Other links and lift over

dbSNP: rs121434606; hg19: chr11-114121104;