Variant 18-48039916-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001318841.2(ZBTB7C):c.1192G>A(p.Glu398Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,460,604 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: 0.000010 ( 0 hom. )

Consequence

ZBTB7C
NM_001318841.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.15

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 Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB7C	NM_001318841.2 linkuse as main transcript	c.1192G>A	p.Glu398Lys	missense_variant	4/5	ENST00000590800.6	NP_001305770.1	A1YPR0B2RG49

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZBTB7C	ENST00000590800.6 linkuse as main transcript	c.1192G>A	p.Glu398Lys	missense_variant	4/5	1	NM_001318841.2	ENSP00000467877.1	A1YPR0
ZBTB7C	ENST00000535628.6 linkuse as main transcript	c.1192G>A	p.Glu398Lys	missense_variant	2/3	1		ENSP00000439781.1	A1YPR0
ZBTB7C	ENST00000586438.5 linkuse as main transcript	c.1192G>A	p.Glu398Lys	missense_variant	2/3	1		ENSP00000468254.1	A1YPR0
ZBTB7C	ENST00000588982.5 linkuse as main transcript	c.1192G>A	p.Glu398Lys	missense_variant	3/4	1		ENSP00000468782.1	A1YPR0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000800

AC:

AN:

249862

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135198

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1460604

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726676

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000479

Hom.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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.1192G>A (p.E398K) alteration is located in exon 2 (coding exon 1) of the ZBTB7C gene. This alteration results from a G to A substitution at nucleotide position 1192, causing the glutamic acid (E) at amino acid position 398 to be replaced by a lysine (K). 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

0.82

BayesDel_addAF

Benign

-0.0038

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

T;T;T;T

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.93

.;.;.;D

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.48

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.16

N;N;N;N

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

0.19

N;.;.;.

REVEL

Benign

0.26

Sift

Benign

0.31

T;.;.;.

Sift4G

Benign

0.57

T;T;T;T

Polyphen

0.68

P;P;P;P

Vest4

0.76

MutPred

0.67

Gain of methylation at E398 (P = 1e-04);Gain of methylation at E398 (P = 1e-04);Gain of methylation at E398 (P = 1e-04);Gain of methylation at E398 (P = 1e-04);

MVP

0.28

MPC

0.50

ClinPred

0.26

GERP RS

5.5

Varity_R

0.45

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.29

Position offset: -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