chr3-179333428-C-T

Variant summary

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

The NM_001303426.2(ZNF639):​c.464C>T​(p.Thr155Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. T155R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF639
NM_001303426.2 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.74
Variant links:
Genes affected
ZNF639 (HGNC:30950): (zinc finger protein 639) This gene encodes a member of the Kruppel-like zinc finger family of proteins. Amplification and overexpression of this gene have been observed in esophageal squamous cell carcinoma. The encoded protein has been shown to bind DNA in a sequence-specific manner and may regulate HIV-1 gene expression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

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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=0.1393565).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF639NM_001303426.2 linkc.464C>T p.Thr155Ile missense_variant Exon 6 of 6 ENST00000496856.6 NP_001290355.1 Q9UID6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF639ENST00000496856.6 linkc.464C>T p.Thr155Ile missense_variant Exon 6 of 6 1 NM_001303426.2 ENSP00000417740.1 Q9UID6

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461862
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727230
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.027
T;T;T;T;T;T
Eigen
Benign
0.058
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.77
.;T;.;T;.;T
M_CAP
Benign
0.0010
T
MetaRNN
Benign
0.14
T;T;T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.90
L;.;L;.;L;L
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
0.12
N;D;N;N;N;.
REVEL
Benign
0.057
Sift
Benign
0.43
T;D;T;D;T;.
Sift4G
Benign
0.24
T;T;T;T;T;T
Polyphen
0.15
B;.;B;.;B;B
Vest4
0.14
MutPred
0.27
Gain of glycosylation at Y151 (P = 0.0089);Gain of glycosylation at Y151 (P = 0.0089);Gain of glycosylation at Y151 (P = 0.0089);Gain of glycosylation at Y151 (P = 0.0089);Gain of glycosylation at Y151 (P = 0.0089);Gain of glycosylation at Y151 (P = 0.0089);
MVP
0.31
MPC
0.20
ClinPred
0.40
T
GERP RS
5.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.056
gMVP
0.33

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: chr3-179051216; API