NM_014872.3:c.839C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014872.3(ZBTB5):​c.839C>T​(p.Ala280Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. A280D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZBTB5
NM_014872.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.70
Variant links:
Genes affected
ZBTB5 (HGNC:23836): (zinc finger and BTB domain containing 5) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.046277493).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZBTB5NM_014872.3 linkc.839C>T p.Ala280Val missense_variant Exon 2 of 2 ENST00000307750.5 NP_055687.1 O15062Q5T942
ZBTB5XM_005251634.3 linkc.839C>T p.Ala280Val missense_variant Exon 2 of 2 XP_005251691.1 O15062Q5T942

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZBTB5ENST00000307750.5 linkc.839C>T p.Ala280Val missense_variant Exon 2 of 2 1 NM_014872.3 ENSP00000307604.4 O15062

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251298
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135834
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
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:
0.00000137
AC:
2
AN:
1461860
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
16
DANN
Benign
0.93
DEOGEN2
Benign
0.0051
T
Eigen
Benign
-0.90
Eigen_PC
Benign
-0.79
FATHMM_MKL
Benign
0.57
D
LIST_S2
Benign
0.71
T
M_CAP
Benign
0.0046
T
MetaRNN
Benign
0.046
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.69
N
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.33
N
REVEL
Benign
0.031
Sift
Benign
0.18
T
Sift4G
Benign
0.25
T
Polyphen
0.012
B
Vest4
0.090
MutPred
0.17
Gain of loop (P = 0.0435);
MVP
0.068
MPC
0.25
ClinPred
0.046
T
GERP RS
2.8
Varity_R
0.047
gMVP
0.098

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: rs756211364; hg19: chr9-37441710; API