Variant 1-6585950-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005341.4(ZBTB48):c.964C>T(p.Pro322Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: 0.0000014 ( 0 hom. )

Consequence

ZBTB48
NM_005341.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.233

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.046907395).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB48	NM_005341.4 linkuse as main transcript	c.964C>T	p.Pro322Ser	missense_variant	4/11	ENST00000377674.9	NP_005332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZBTB48	ENST00000377674.9 linkuse as main transcript	c.964C>T	p.Pro322Ser	missense_variant	4/11	1	NM_005341.4	ENSP00000366902	P1
ZBTB48	ENST00000482360.5 linkuse as main transcript	n.649C>T		non_coding_transcript_exon_variant	1/7	1
ZBTB48	ENST00000488936.1 linkuse as main transcript	c.229C>T	p.Pro77Ser	missense_variant	3/7	3		ENSP00000466390

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251448

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135892

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461790

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

8.99e-7

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

Oct 27, 2022

The c.964C>T (p.P322S) alteration is located in exon 4 (coding exon 3) of the ZBTB48 gene. This alteration results from a C to T substitution at nucleotide position 964, causing the proline (P) at amino acid position 322 to be replaced by a serine (S). 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

0.13

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.046

T;.

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.27

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.0031

MetaRNN

Benign

0.047

T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

0.98

PrimateAI

Uncertain

0.62

PROVEAN

Benign

0.74

N;.

REVEL

Benign

0.048

Sift

Benign

0.76

T;.

Sift4G

Benign

0.74

T;T

Polyphen

0.0

B;.

Vest4

0.27

MutPred

0.42

Loss of glycosylation at K323 (P = 0.1061);.;

MVP

0.043

MPC

0.38

ClinPred

0.070

GERP RS

3.4

Varity_R

0.044

gMVP

0.20

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