Genetic Variant ZBTB47:p.Pro119Leu (chr3-42658711-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_145166.4(ZBTB47):c.356C>T(p.Pro119Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000221 in 1,535,354 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 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

ZBTB47
NM_145166.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.70

Variant links:

Genes affected

ZBTB47 (HGNC:26955): (zinc finger and BTB domain containing 47) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB47 links:

Genome browser will be placed here

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=0.049179703).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB47	NM_145166.4 link	c.356C>T	p.Pro119Leu	missense_variant	Exon 2 of 6	ENST00000232974.11	NP_660149.2	Q9UFB7-1
ZBTB47	NM_001410746.1 link	c.440C>T	p.Pro147Leu	missense_variant	Exon 2 of 6		NP_001397675.1
ZBTB47	XM_047449234.1 link	c.536C>T	p.Pro179Leu	missense_variant	Exon 3 of 7		XP_047305190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZBTB47	ENST00000232974.11 link	c.356C>T	p.Pro119Leu	missense_variant	Exon 2 of 6	5	NM_145166.4	ENSP00000232974.6	Q9UFB7-1
ZBTB47	ENST00000680014.1 link	c.440C>T	p.Pro147Leu	missense_variant	Exon 2 of 6			ENSP00000504903.1	A0A7P0T820
ZBTB47	ENST00000505904.1 link	c.-421C>T		upstream_gene_variant		5		ENSP00000420968.1	D6RDG5

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000313

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000644

AC:

AN:

139738

Hom.:

AF XY:

0.0000665

AC XY:

AN XY:

75178

show subpopulations

Gnomad AFR exome

AF:

0.000282

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000474

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000160

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000152

AC:

AN:

1382982

Hom.:

Cov.:

AF XY:

0.0000132

AC XY:

AN XY:

682374

show subpopulations

Gnomad4 AFR exome

AF:

0.000127

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000224

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.0000295

Gnomad4 NFE exome

AF:

0.00000464

Gnomad4 OTH exome

AF:

0.0000346

GnomAD4 genome

AF:

0.0000853

AC:

AN:

152372

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000718

ExAC

AF:

0.0000429

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.356C>T (p.P119L) alteration is located in exon 2 (coding exon 1) of the ZBTB47 gene. This alteration results from a C to T substitution at nucleotide position 356, causing the proline (P) at amino acid position 119 to be replaced by a leucine (L). 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

-0.49

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.64

M_CAP

Benign

0.016

MetaRNN

Benign

0.049

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-2.2

REVEL

Benign

0.14

Sift

Benign

0.037

Sift4G

Uncertain

0.043

Vest4

0.058

MutPred

0.46

Loss of glycosylation at P119 (P = 0.0131);

MVP

0.10

MPC

0.86

ClinPred

0.036

GERP RS

3.9

Varity_R

0.058

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