Variant 11-10853021-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000413761.7(ZBED5):c.1925A>G(p.His642Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,352 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZBED5
ENST00000413761.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60

Variant links:

Genes affected

ZBED5 (HGNC:30803): (zinc finger BED-type containing 5) This gene is unusual in that its coding sequence is mostly derived from Charlie-like DNA transposon; however, it does not appear to be an active DNA transposon as it is not flanked by terminal inverted repeats. The encoded protein is conserved among the mammalian Laurasiatheria branch. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jan 2009]

ZBED5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBED5	NM_001143667.2 linkuse as main transcript	c.1925A>G	p.His642Arg	missense_variant	3/3	ENST00000413761.7	NP_001137139.1
ZBED5	NM_021211.4 linkuse as main transcript	c.1925A>G	p.His642Arg	missense_variant	3/3		NP_067034.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZBED5	ENST00000413761.7 linkuse as main transcript	c.1925A>G	p.His642Arg	missense_variant	3/3	1	NM_001143667.2	ENSP00000415939	P1
ZBED5	ENST00000432999.6 linkuse as main transcript	c.1925A>G	p.His642Arg	missense_variant	3/3	1		ENSP00000398106	P1
ZBED5	ENST00000525350.5 linkuse as main transcript	n.75+3123A>G		intron_variant, non_coding_transcript_variant		2
ZBED5	ENST00000533925.5 linkuse as main transcript	n.327-2918A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1399352

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690176

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000185

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

Nov 29, 2023

The c.1925A>G (p.H642R) alteration is located in exon 3 (coding exon 1) of the ZBED5 gene. This alteration results from a A to G substitution at nucleotide position 1925, causing the histidine (H) at amino acid position 642 to be replaced by an arginine (R). 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

0.12

BayesDel_addAF

Benign

-0.0025

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.089

T;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.048

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.72

.;T

M_CAP

Benign

0.0033

MetaRNN

Uncertain

0.57

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

0.89

N;N

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.1

D;D

REVEL

Benign

0.24

Sift

Uncertain

0.011

D;D

Sift4G

Uncertain

0.051

T;T

Polyphen

0.37

B;B

Vest4

0.60

MutPred

0.79

Gain of MoRF binding (P = 0.0273);Gain of MoRF binding (P = 0.0273);

MVP

0.13

ClinPred

0.29

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.62

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