Variant 18-48029666-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001318841.2(ZBTB7C):c.1454C>G(p.Ala485Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000142 in 1,412,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZBTB7C
NM_001318841.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.90

Variant links:

Genes affected

ZBTB7C (HGNC:31700): (zinc finger and BTB domain containing 7C) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of cell population proliferation. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB7C links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16667166).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB7C	NM_001318841.2 linkuse as main transcript	c.1454C>G	p.Ala485Gly	missense_variant	5/5	ENST00000590800.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZBTB7C	ENST00000590800.6 linkuse as main transcript	c.1454C>G	p.Ala485Gly	missense_variant	5/5	1	NM_001318841.2	P1
ZBTB7C	ENST00000535628.6 linkuse as main transcript	c.1454C>G	p.Ala485Gly	missense_variant	3/3	1		P1
ZBTB7C	ENST00000586438.5 linkuse as main transcript	c.1454C>G	p.Ala485Gly	missense_variant	3/3	1		P1
ZBTB7C	ENST00000588982.5 linkuse as main transcript	c.1454C>G	p.Ala485Gly	missense_variant	4/4	1		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000118

AC:

AN:

169410

Hom.:

AF XY:

0.0000107

AC XY:

AN XY:

93886

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000276

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1412750

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

700448

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000183

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000172

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2022

The c.1454C>G (p.A485G) alteration is located in exon 3 (coding exon 2) of the ZBTB7C gene. This alteration results from a C to G substitution at nucleotide position 1454, causing the alanine (A) at amino acid position 485 to be replaced by a glycine (G). 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

Benign

0.16

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.46

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.015

T;T;T;T

Eigen

Benign

0.080

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.96

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;L;L;L

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.6

N;.;.;.

REVEL

Benign

0.062

Sift

Uncertain

0.0030

D;.;.;.

Sift4G

Benign

0.067

T;T;T;T

Polyphen

0.54

P;P;P;P

Vest4

0.19

MutPred

0.20

Loss of stability (P = 0.0371);Loss of stability (P = 0.0371);Loss of stability (P = 0.0371);Loss of stability (P = 0.0371);

MVP

0.068

MPC

1.1

ClinPred

0.83

GERP RS

4.5

Varity_R

0.34

gMVP

0.33

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over