chr1-203797565-C-T

Variant summary

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

The NM_001395895.1(ZBED6):​c.43C>T​(p.Pro15Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000725 in 1,378,932 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 (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

ZBED6
NM_001395895.1 missense

Scores

2
1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.465
Variant links:
Genes affected
ZBED6 (HGNC:33273): (zinc finger BED-type containing 6) The protein encoded by this transposon-derived intronless gene is a transcriptional repressor that binds to the consensus sequence 5'-GCTCGC-3'. The encoded protein has been shown to repress IGF2 transcription. This gene is located within the first intron of the ZC3H11A gene. [provided by RefSeq, Jul 2016]
ZC3H11A (HGNC:29093): (zinc finger CCCH-type containing 11A) Enables RNA binding activity. Involved in poly(A)+ mRNA export from nucleus. Colocalizes with transcription export complex. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.07894814).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZBED6NM_001395895.1 linkc.43C>T p.Pro15Ser missense_variant Exon 1 of 17 ENST00000550078.3 NP_001382824.1
ZC3H11ANM_001376342.1 linkc.-1588+1771C>T intron_variant Intron 1 of 17 ENST00000367210.3 NP_001363271.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZBED6ENST00000550078.3 linkc.43C>T p.Pro15Ser missense_variant Exon 1 of 17 1 NM_001395895.1 ENSP00000447879.1 P86452
ZC3H11AENST00000367210.3 linkc.-1588+1771C>T intron_variant Intron 1 of 17 1 NM_001376342.1 ENSP00000356179.1 O75152

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.25e-7
AC:
1
AN:
1378932
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
680256
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:
9.28e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 27, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.43C>T (p.P15S) alteration is located in exon 1 (coding exon 1) of the ZBED6 gene. This alteration results from a C to T substitution at nucleotide position 43, causing the proline (P) at amino acid position 15 to be replaced by a serine (S). 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
0.083
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
16
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0021
T
Eigen
Benign
-0.36
Eigen_PC
Benign
-0.31
FATHMM_MKL
Benign
0.66
D
LIST_S2
Benign
0.48
T
M_CAP
Benign
0.0093
T
MetaRNN
Benign
0.079
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.48
N
REVEL
Benign
0.056
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Vest4
0.031
MutPred
0.21
Gain of phosphorylation at P15 (P = 0.0286);
MVP
0.055
ClinPred
0.16
T
GERP RS
3.4
Varity_R
0.091
gMVP
0.089

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.

Other links and lift over

dbSNP: rs1668971486; hg19: chr1-203766693; API