11-10853051-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000413761.7(ZBED5):ā€‹c.1895T>Cā€‹(p.Val632Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,399,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

ZBED5
ENST00000413761.7 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22
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]

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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=0.24741387).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZBED5NM_001143667.2 linkuse as main transcriptc.1895T>C p.Val632Ala missense_variant 3/3 ENST00000413761.7 NP_001137139.1
ZBED5NM_021211.4 linkuse as main transcriptc.1895T>C p.Val632Ala missense_variant 3/3 NP_067034.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZBED5ENST00000413761.7 linkuse as main transcriptc.1895T>C p.Val632Ala missense_variant 3/31 NM_001143667.2 ENSP00000415939 P1
ZBED5ENST00000432999.6 linkuse as main transcriptc.1895T>C p.Val632Ala missense_variant 3/31 ENSP00000398106 P1
ZBED5ENST00000525350.5 linkuse as main transcriptn.75+3093T>C intron_variant, non_coding_transcript_variant 2
ZBED5ENST00000533925.5 linkuse as main transcriptn.327-2948T>C intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000652
AC:
1
AN:
153444
Hom.:
0
AF XY:
0.0000123
AC XY:
1
AN XY:
81098
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000884
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000214
AC:
3
AN:
1399304
Hom.:
0
Cov.:
31
AF XY:
0.00000290
AC XY:
2
AN XY:
690142
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000560
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000280
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.:
32

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 submitterclinical testingAmbry GeneticsMay 12, 2024The c.1895T>C (p.V632A) alteration is located in exon 3 (coding exon 1) of the ZBED5 gene. This alteration results from a T to C substitution at nucleotide position 1895, causing the valine (V) at amino acid position 632 to be replaced by an alanine (A). 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
0.33
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
20
DANN
Benign
0.97
DEOGEN2
Benign
0.034
T;T
Eigen
Benign
-0.21
Eigen_PC
Benign
-0.20
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Benign
0.57
.;T
M_CAP
Benign
0.0044
T
MetaRNN
Benign
0.25
T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.57
N;N
MutationTaster
Benign
0.99
N;N
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-2.3
N;N
REVEL
Benign
0.094
Sift
Uncertain
0.0080
D;D
Sift4G
Uncertain
0.010
D;D
Polyphen
0.83
P;P
Vest4
0.37
MutPred
0.60
Loss of stability (P = 0.0578);Loss of stability (P = 0.0578);
MVP
0.072
ClinPred
0.15
T
GERP RS
2.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.075
gMVP
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs1178128619; hg19: chr11-10874598; API