rs931412101

Variant names:

• chr3-101652832-T-G
• rs931412101
• NM_014415.4:c.2416A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014415.4(ZBTB11):​c.2416A>C​(p.Lys806Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,774 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZBTB11 NM_014415.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.60
• Publications: 0 publications found

Genes affected

ZBTB11 (HGNC:16740): (zinc finger and BTB domain containing 11) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Located in nucleoplasm. Implicated in autosomal recessive non-syndromic intellectual disability. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB11 Gene-Disease associations (from GenCC):

• intellectual developmental disorder, autosomal recessive 69

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014415.4. 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
	ZBTB11	NM_014415.4	MANE Select	c.2416A>C	p.Lys806Gln	missense	Exon 9 of 11	NP_055230.2	O95625

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB11	ENST00000312938.5	TSL:1 MANE Select	c.2416A>C	p.Lys806Gln	missense	Exon 9 of 11	ENSP00000326200.4	O95625
	ZBTB11	ENST00000704111.1		c.2170A>C	p.Lys724Gln	missense	Exon 8 of 10	ENSP00000515702.1	A0A994J7A5
	ZBTB11	ENST00000688910.1		c.2014A>C	p.Lys672Gln	missense	Exon 9 of 11	ENSP00000510736.1	A0A8I5KRR0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461774 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727180

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111974

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.064	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.0	L
PhyloP100		7.6
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.27
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.041	D
Polyphen		1.0	D
Vest4		0.51
MutPred		0.50		Loss of methylation at K806 (P = 0.0114)
MVP		0.61
MPC		2.0
ClinPred		0.91	D
GERP RS		4.9
Varity_R		0.29
gMVP		0.59
Mutation Taster		=33/67	disease causing

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: rs931412101; hg19: chr3-101371676;