Variant 18-48029330-G-A 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.1790C>T(p.Ala597Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZBTB7C
NM_001318841.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.31

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:

Genome browser will be placed here

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=0.0956938).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB7C	NM_001318841.2 linkuse as main transcript	c.1790C>T	p.Ala597Val	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.1790C>T	p.Ala597Val	missense_variant	5/5	1	NM_001318841.2	P1
ZBTB7C	ENST00000535628.6 linkuse as main transcript	c.1790C>T	p.Ala597Val	missense_variant	3/3	1		P1
ZBTB7C	ENST00000586438.5 linkuse as main transcript	c.1790C>T	p.Ala597Val	missense_variant	3/3	1		P1
ZBTB7C	ENST00000588982.5 linkuse as main transcript	c.1790C>T	p.Ala597Val	missense_variant	4/4	1		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1388688

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

686556

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 05, 2024

The c.1790C>T (p.A597V) alteration is located in exon 3 (coding exon 2) of the ZBTB7C gene. This alteration results from a C to T substitution at nucleotide position 1790, causing the alanine (A) at amino acid position 597 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

Benign

0.20

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

Cadd

Benign

Dann

Benign

0.95

DEOGEN2

Benign

0.0046

T;T;T;T

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.65

M_CAP

Benign

0.036

MetaRNN

Benign

0.096

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;N;N;N

MutationTaster

Benign

0.95

N;N;N;N;N

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.090

N;.;.;.

REVEL

Benign

0.080

Sift

Benign

0.32

T;.;.;.

Sift4G

Benign

0.67

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.20

MutPred

0.30

Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);

MVP

0.043

MPC

0.45

ClinPred

0.41

GERP RS

3.4

Varity_R

0.071

gMVP

0.41

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over