Genetic Variant ZBED3:p.Gln75Leu (chr5-77077655-T-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032367.4(ZBED3):c.224A>T(p.Gln75Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZBED3
NM_032367.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0390

Variant links:

Genes affected

ZBED3 (HGNC:20711): (zinc finger BED-type containing 3) This gene belongs to a class of genes that arose through hAT DNA transposition and that encode regulatory proteins. This gene is upregulated in lung cancer tissues, where the encoded protein causes an accumulation of beta-catenin and enhanced lung cancer cell invasion. In addition, the encoded protein can be secreted and be involved in resistance to insulin. [provided by RefSeq, Jul 2016]

ZBED3 links:

ENSG00000285000 (HGNC:):

ENSG00000285000 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35652405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBED3	NM_032367.4 link	c.224A>T	p.Gln75Leu	missense_variant	Exon 3 of 3	ENST00000255198.3	NP_115743.1	Q96IU2
ZBED3	NM_001329564.2 link	c.224A>T	p.Gln75Leu	missense_variant	Exon 2 of 2		NP_001316493.1	Q96IU2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZBED3	ENST00000255198.3 link	c.224A>T	p.Gln75Leu	missense_variant	Exon 3 of 3	1	NM_032367.4	ENSP00000255198.2	Q96IU2
ENSG00000285000	ENST00000646704.1 link	n.1809+15853T>A		intron_variant	Intron 13 of 15			ENSP00000495089.1	A0A2R8YFF1
ZBED3	ENST00000511587.1 link	c.224A>T	p.Gln75Leu	missense_variant	Exon 2 of 2	3		ENSP00000427487.1	D6RIC4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1259220

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

619624

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:

0.00

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

Nov 17, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.224A>T (p.Q75L) alteration is located in exon 3 (coding exon 1) of the ZBED3 gene. This alteration results from a A to T substitution at nucleotide position 224, causing the glutamine (Q) at amino acid position 75 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

0.26

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.53

T;T

M_CAP

Pathogenic

0.61

MetaRNN

Benign

0.36

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

L;.

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-4.7

D;D

REVEL

Benign

0.079

Sift

Benign

0.043

D;D

Sift4G

Benign

0.10

T;.

Polyphen

0.041

B;.

Vest4

0.22

MutPred

0.64

Loss of catalytic residue at Q75 (P = 0.0276);Loss of catalytic residue at Q75 (P = 0.0276);

MVP

0.30

MPC

1.4

ClinPred

0.94

GERP RS

2.2

Varity_R

0.30

gMVP

0.17

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over