Variant chr18-48029610-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001318841.2(ZBTB7C):c.1510G>A(p.Ala504Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000215 in 1,487,090 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

ZBTB7C
NM_001318841.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.383

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03076002).

BS2

High AC in GnomAdExome4 at 29 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB7C	NM_001318841.2 linkuse as main transcript	c.1510G>A	p.Ala504Thr	missense_variant	5/5	ENST00000590800.6	NP_001305770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZBTB7C	ENST00000590800.6 linkuse as main transcript	c.1510G>A	p.Ala504Thr	missense_variant	5/5	1	NM_001318841.2	ENSP00000467877	P1
ZBTB7C	ENST00000535628.6 linkuse as main transcript	c.1510G>A	p.Ala504Thr	missense_variant	3/3	1		ENSP00000439781	P1
ZBTB7C	ENST00000586438.5 linkuse as main transcript	c.1510G>A	p.Ala504Thr	missense_variant	3/3	1		ENSP00000468254	P1
ZBTB7C	ENST00000588982.5 linkuse as main transcript	c.1510G>A	p.Ala504Thr	missense_variant	4/4	1		ENSP00000468782	P1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000645

AC:

AN:

93092

Hom.:

AF XY:

0.0000579

AC XY:

AN XY:

51792

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000498

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000309

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000217

AC:

AN:

1334946

Hom.:

Cov.:

AF XY:

0.0000274

AC XY:

AN XY:

657278

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000617

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000568

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000659

Gnomad4 OTH exome

AF:

0.0000903

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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 14, 2023

The c.1510G>A (p.A504T) alteration is located in exon 3 (coding exon 2) of the ZBTB7C gene. This alteration results from a G to A substitution at nucleotide position 1510, causing the alanine (A) at amino acid position 504 to be replaced by a threonine (T). 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

0.15

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

T;T;T;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.65

.;.;.;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.031

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

N;N;N;N

MutationTaster

Benign

0.67

N;N;N;N;N

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.21

N;.;.;.

REVEL

Benign

0.013

Sift

Benign

0.10

T;.;.;.

Sift4G

Benign

0.73

T;T;T;T

Polyphen

0.0010

B;B;B;B

Vest4

0.058

MutPred

0.40

Gain of glycosylation at A504 (P = 0.0287);Gain of glycosylation at A504 (P = 0.0287);Gain of glycosylation at A504 (P = 0.0287);Gain of glycosylation at A504 (P = 0.0287);

MVP

0.068

MPC

0.39

ClinPred

0.067

GERP RS

3.0

Varity_R

0.041

gMVP

0.31

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