8-80487043-A-T

Position:

• chr8-80487043-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001105539.3(ZBTB10):​c.233A>T​(p.Glu78Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: ZBTB10 NM_001105539.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.12

Genes affected

ZBTB10 (HGNC:30953): (zinc finger and BTB domain containing 10) Predicted to enable RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29972324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB10	NM_001105539.3	c.233A>T	p.Glu78Val	missense_variant	1/6	ENST00000455036.8	NP_001099009.1
ZBTB10	NM_023929.5	c.233A>T	p.Glu78Val	missense_variant	1/7		NP_076418.3
ZBTB10	NM_001277145.2	c.96+1164A>T		intron_variant			NP_001264074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB10	ENST00000455036.8	c.233A>T	p.Glu78Val	missense_variant	1/6	2	NM_001105539.3	ENSP00000412036.3
ZBTB10	ENST00000430430.5	c.233A>T	p.Glu78Val	missense_variant	2/7	5		ENSP00000387462.1
ZBTB10	ENST00000426744.5	c.233A>T	p.Glu78Val	missense_variant	1/7	5		ENSP00000416134.2
ZBTB10	ENST00000379091.8	c.96+1164A>T		intron_variant		2		ENSP00000368384.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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

Aug 16, 2021

The c.233A>T (p.E78V) alteration is located in exon 1 (coding exon 1) of the ZBTB10 gene. This alteration results from a A to T substitution at nucleotide position 233, causing the glutamic acid (E) at amino acid position 78 to be replaced by a valine (V). 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	Uncertain	0.34
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0068	T;T;.
Eigen	Benign	0.042
Eigen_PC	Benign	0.019
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.66	.;T;T
M_CAP	Pathogenic	0.61	D
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N;N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.50	N;N;N
REVEL	Benign	0.10
Sift	Uncertain	0.0020	D;D;D
Sift4G	Benign	0.18	T;T;T
Polyphen		0.99	D;D;D
Vest4		0.27
MutPred		0.19		Loss of solvent accessibility (P = 0.0062);Loss of solvent accessibility (P = 0.0062);Loss of solvent accessibility (P = 0.0062);
MVP		0.068
MPC		1.8
ClinPred		0.66	D
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.25
gMVP		0.30

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: chr8-81399278;