Genetic Variant NM_032367.4:c.221A>T (chr5-77077658-T-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_032367.4(ZBED3):c.221A>T(p.Glu74Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,405,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E74Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 8.0e-7 ( 0 hom. )

Consequence

ZBED3
NM_032367.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.564

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3215923).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032367.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBED3	NM_032367.4	MANE Select	c.221A>T	p.Glu74Val	missense	Exon 3 of 3	NP_115743.1	Q96IU2
	ZBED3	NM_001329564.2		c.221A>T	p.Glu74Val	missense	Exon 2 of 2	NP_001316493.1	Q96IU2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZBED3	ENST00000255198.3	TSL:1 MANE Select	c.221A>T	p.Glu74Val	missense	Exon 3 of 3	ENSP00000255198.2	Q96IU2
ENSG00000285000	ENST00000646704.1		n.1809+15856T>A		intron	N/A	ENSP00000495089.1	A0A2R8YFF1
ZBED3	ENST00000896398.1		c.221A>T	p.Glu74Val	missense	Exon 4 of 4	ENSP00000566457.1

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151390

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000196

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

GnomAD4 exome

AF:

7.98e-7

AC:

AN:

1253712

Hom.:

Cov.:

AF XY:

0.00000162

AC XY:

AN XY:

616650

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25398

American (AMR)

AF:

0.00

AC:

AN:

20178

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20720

East Asian (EAS)

AF:

0.00

AC:

AN:

27094

South Asian (SAS)

AF:

0.00

AC:

AN:

62158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30312

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3596

European-Non Finnish (NFE)

AF:

9.87e-7

AC:

AN:

1013084

Other (OTH)

AF:

0.00

AC:

AN:

51172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151390

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73922

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41296

American (AMR)

AF:

0.00

AC:

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000196

AC:

AN:

5092

South Asian (SAS)

AF:

0.00

AC:

AN:

4792

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67804

Other (OTH)

AF:

0.00

AC:

AN:

2084

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.062

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.019

Eigen

Benign

-0.0023

Eigen_PC

Benign

-0.027

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.34

M_CAP

Pathogenic

0.52

MetaRNN

Benign

0.32

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

0.56

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.089

Sift

Benign

0.079

Sift4G

Benign

0.087

Polyphen

0.97

Vest4

0.28

MutPred

0.51

Gain of sheet (P = 0.0221)

MVP

0.37

MPC

2.6

ClinPred

0.75

GERP RS

3.5

Varity_R

0.15

gMVP

0.23

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over