Variant 1-6586708-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000377674.9(ZBTB48):c.1058C>G(p.Ser353Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000078 in 1,410,838 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000078 ( 0 hom. )

Consequence

ZBTB48
ENST00000377674.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.40

Variant links:

Genes affected

ZBTB48 (HGNC:4930): (zinc finger and BTB domain containing 48) Enables double-stranded telomeric DNA binding activity; identical protein binding activity; and transcription cis-regulatory region binding activity. Involved in positive regulation of transcription, DNA-templated and telomere maintenance via telomere lengthening. Located in chromosome, telomeric region. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB48 links:

ZBTB48 (HGNC:):

ZBTB48 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB48	NM_005341.4 linkuse as main transcript	c.1058C>G	p.Ser353Cys	missense_variant	5/11	ENST00000377674.9	NP_005332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZBTB48	ENST00000377674.9 linkuse as main transcript	c.1058C>G	p.Ser353Cys	missense_variant	5/11	1	NM_005341.4	ENSP00000366902.4	P10074
ZBTB48	ENST00000482360.5 linkuse as main transcript	n.1407C>G		non_coding_transcript_exon_variant	1/7	1
ZBTB48	ENST00000488936.1 linkuse as main transcript	c.323C>G	p.Ser108Cys	missense_variant	4/7	3		ENSP00000466390.1	K7EM76
ZBTB48	ENST00000498342.5 linkuse as main transcript	n.502C>G		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000142

AC:

AN:

211838

Hom.:

AF XY:

0.0000177

AC XY:

AN XY:

112946

show subpopulations

Gnomad AFR exome

AF:

0.000127

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:

0.0000103

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000780

AC:

AN:

1410838

Hom.:

Cov.:

AF XY:

0.0000101

AC XY:

AN XY:

695798

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:

0.0000101

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000165

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

Aug 28, 2023

The c.1058C>G (p.S353C) alteration is located in exon 5 (coding exon 4) of the ZBTB48 gene. This alteration results from a C to G substitution at nucleotide position 1058, causing the serine (S) at amino acid position 353 to be replaced by a cysteine (C). 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

0.23

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

T;.

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.036

MetaRNN

Uncertain

0.45

T;T

MetaSVM

Uncertain

-0.21

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.9

D;.

REVEL

Benign

0.26

Sift

Uncertain

0.019

D;.

Sift4G

Uncertain

0.038

D;D

Polyphen

0.99

D;.

Vest4

0.51

MVP

0.22

MPC

1.1

ClinPred

0.87

GERP RS

5.3

Varity_R

0.18

gMVP

0.23

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