3-101676880-C-G

Position:

• chr3-101676880-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014415.4(ZBTB11):​c.35G>C​(p.Arg12Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZBTB11 NM_014415.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.23

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]

LOC124906262 (HGNC:):

ZBTB11-AS1 (HGNC:48573): (ZBTB11 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB11	NM_014415.4	c.35G>C	p.Arg12Pro	missense_variant	1/11	ENST00000312938.5	NP_055230.2
LOC124906262	XM_047449411.1	c.-3843C>G		5_prime_UTR_variant	1/3		XP_047305367.1
ZBTB11-AS1	NR_024407.1	n.451C>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB11	ENST00000312938.5	c.35G>C	p.Arg12Pro	missense_variant	1/11	1	NM_014415.4	ENSP00000326200	P1
ZBTB11-AS1	ENST00000609682.2	n.457C>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 23, 2022

The c.35G>C (p.R12P) alteration is located in exon 1 (coding exon 1) of the ZBTB11 gene. This alteration results from a G to C substitution at nucleotide position 35, causing the arginine (R) at amino acid position 12 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	T;.
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.63	N;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.9	N;D
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.094	T;T
Polyphen		0.27	B;P
Vest4		0.83
MutPred		0.43		Gain of glycosylation at T15 (P = 0.0093);Gain of glycosylation at T15 (P = 0.0093);
MVP		0.73
MPC		2.6
ClinPred		0.91	D
GERP RS		5.7
Varity_R		0.62
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-101395724;