Variant chr4-4302665-C-G 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_145291.4(ZBTB49):c.829C>G(p.Leu277Val) 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 1,457,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZBTB49
NM_145291.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.124

Variant links:

Genes affected

ZBTB49 (HGNC:19883): (zinc finger and BTB domain containing 49) Enables DNA-binding transcription factor binding activity; sequence-specific DNA binding activity; and transcription coactivator binding activity. Involved in negative regulation of cell population proliferation; positive regulation of transcription by RNA polymerase II; and regulation of cell cycle. Located in cytosol; microtubule cytoskeleton; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB49 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=0.076906025).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB49	NM_145291.4 linkuse as main transcript	c.829C>G	p.Leu277Val	missense_variant	3/8	ENST00000337872.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB49	ENST00000337872.9 linkuse as main transcript	c.829C>G	p.Leu277Val	missense_variant	3/8	1	NM_145291.4	P1	Q6ZSB9-1
ZBTB49	ENST00000504302.1 linkuse as main transcript	c.40C>G	p.Leu14Val	missense_variant	1/2	1
ZBTB49	ENST00000515012.5 linkuse as main transcript	c.829C>G	p.Leu277Val	missense_variant, NMD_transcript_variant	3/6	1
ZBTB49	ENST00000503703.5 linkuse as main transcript	c.*72C>G		3_prime_UTR_variant, NMD_transcript_variant	3/7	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457894

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724844

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

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 27, 2023

The c.829C>G (p.L277V) alteration is located in exon 3 (coding exon 2) of the ZBTB49 gene. This alteration results from a C to G substitution at nucleotide position 829, causing the leucine (L) at amino acid position 277 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

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0020

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.75

M_CAP

Benign

0.0045

MetaRNN

Benign

0.077

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

0.67

D;D;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.55

REVEL

Benign

0.014

Sift

Benign

0.090

Sift4G

Benign

0.090

Polyphen

0.41

Vest4

0.076

MutPred

0.41

Loss of glycosylation at S274 (P = 0.0663);

MVP

0.38

MPC

0.17

ClinPred

0.19

GERP RS

2.4

Varity_R

0.055

gMVP

0.10

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