1-40451005-C-T

Variant summary

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

The NM_023070.3(ZFP69B):​c.44C>T​(p.Thr15Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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)

Consequence

ZFP69B
NM_023070.3 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.101
Variant links:
Genes affected
ZFP69B (HGNC:28053): (ZFP69 zinc finger protein B) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in Golgi organization. Located in nucleolus. [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=0.116993755).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZFP69BNM_023070.3 linkc.44C>T p.Thr15Ile missense_variant Exon 1 of 5 ENST00000361584.5 NP_075558.2 Q9UJL9-1
ZFP69BNM_001369565.1 linkc.44C>T p.Thr15Ile missense_variant Exon 2 of 6 NP_001356494.1
ZFP69BXM_005271136.2 linkc.44C>T p.Thr15Ile missense_variant Exon 2 of 6 XP_005271193.1
ZFP69BXM_017002147.2 linkc.44C>T p.Thr15Ile missense_variant Exon 2 of 6 XP_016857636.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZFP69BENST00000361584.5 linkc.44C>T p.Thr15Ile missense_variant Exon 1 of 5 1 NM_023070.3 ENSP00000354547.4 Q9UJL9-1
ZFP69BENST00000484445.5 linkc.44C>T p.Thr15Ile missense_variant Exon 2 of 5 1 ENSP00000435907.1 E9PS66
ZFP69BENST00000411995.6 linkc.44C>T p.Thr15Ile missense_variant Exon 2 of 6 5 ENSP00000399664.2 Q9UJL9-1
ZFP69BENST00000469416.1 linkn.424C>T non_coding_transcript_exon_variant Exon 2 of 5 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
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
Jun 07, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.44C>T (p.T15I) alteration is located in exon 1 (coding exon 1) of the ZFP69B gene. This alteration results from a C to T substitution at nucleotide position 44, causing the threonine (T) at amino acid position 15 to be replaced by an isoleucine (I). 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
0.17
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
13
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0020
.;T;T
Eigen
Benign
-0.88
Eigen_PC
Benign
-0.94
FATHMM_MKL
Benign
0.033
N
LIST_S2
Benign
0.81
T;.;T
M_CAP
Benign
0.0058
T
MetaRNN
Benign
0.12
T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Uncertain
2.1
.;M;M
PrimateAI
Benign
0.31
T
PROVEAN
Uncertain
-2.6
D;N;.
REVEL
Benign
0.011
Sift
Uncertain
0.0060
D;T;.
Sift4G
Uncertain
0.016
D;D;D
Polyphen
0.22
.;B;B
Vest4
0.32
MutPred
0.43
Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);
MVP
0.072
MPC
0.13
ClinPred
0.16
T
GERP RS
1.9
Varity_R
0.042
gMVP
0.15

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.

Other links and lift over

hg19: chr1-40916677; API