3-179334315-G-A

Variant summary

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

The NM_001303426.2(ZNF639):​c.1351G>A​(p.Asp451Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000236 in 1,612,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

ZNF639
NM_001303426.2 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.79
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]

Genome browser will be placed here

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=0.2332696).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF639NM_001303426.2 linkuse as main transcriptc.1351G>A p.Asp451Asn missense_variant 6/6 ENST00000496856.6 NP_001290355.1 Q9UID6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF639ENST00000496856.6 linkuse as main transcriptc.1351G>A p.Asp451Asn missense_variant 6/61 NM_001303426.2 ENSP00000417740.1 Q9UID6
ZNF639ENST00000326361.7 linkuse as main transcriptc.1351G>A p.Asp451Asn missense_variant 7/71 ENSP00000325634.3 Q9UID6
ZNF639ENST00000621687.1 linkuse as main transcriptc.1351G>A p.Asp451Asn missense_variant 4/41 ENSP00000477626.1 Q9UID6
ZNF639ENST00000484866.5 linkuse as main transcriptc.1351G>A p.Asp451Asn missense_variant 5/52 ENSP00000418766.1 Q9UID6

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152174
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
249748
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135268
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000265
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000253
AC:
37
AN:
1460644
Hom.:
0
Cov.:
32
AF XY:
0.0000248
AC XY:
18
AN XY:
726502
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:
0.0000324
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152174
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

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 GeneticsAug 11, 2022The c.1351G>A (p.D451N) alteration is located in exon 7 (coding exon 4) of the ZNF639 gene. This alteration results from a G to A substitution at nucleotide position 1351, causing the aspartic acid (D) at amino acid position 451 to be replaced by an asparagine (N). 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
Pathogenic
0.70
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.63
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0083
T;T;T;T
Eigen
Benign
-0.019
Eigen_PC
Uncertain
0.23
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.90
.;.;.;D
M_CAP
Benign
0.027
D
MetaRNN
Benign
0.23
T;T;T;T
MetaSVM
Benign
-0.54
T
MutationAssessor
Benign
0.46
N;N;N;N
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-0.53
N;N;N;.
REVEL
Benign
0.21
Sift
Benign
0.19
T;T;T;.
Sift4G
Benign
0.18
T;T;T;T
Polyphen
0.15
B;B;B;B
Vest4
0.64
MVP
0.32
MPC
0.65
ClinPred
0.37
T
GERP RS
6.1
Varity_R
0.18
gMVP
0.35

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: rs751257866; hg19: chr3-179052103; API