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GeneBe

1-227654829-G-T

Variant summary

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

The NM_001367909.1(ZNF678):c.579G>T(p.Trp193Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZNF678
NM_001367909.1 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.87
Variant links:
Genes affected
ZNF678 (HGNC:28652): (zinc finger protein 678) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [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=0.087639004).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF678NM_001367909.1 linkuse as main transcriptc.579G>T p.Trp193Cys missense_variant 4/4 ENST00000343776.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF678ENST00000343776.10 linkuse as main transcriptc.579G>T p.Trp193Cys missense_variant 4/41 NM_001367909.1 P1
ZNF678ENST00000397097.4 linkuse as main transcriptc.579G>T p.Trp193Cys missense_variant 2/21 P1
ZNF678ENST00000608949.5 linkuse as main transcriptc.226+353G>T intron_variant 1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000805
AC:
2
AN:
248536
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134480
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:
0.0000178
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1456286
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
724450
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

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 GeneticsNov 29, 2021The c.744G>T (p.W248C) alteration is located in exon 4 (coding exon 4) of the ZNF678 gene. This alteration results from a G to T substitution at nucleotide position 744, causing the tryptophan (W) at amino acid position 248 to be replaced by a cysteine (C). 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
Uncertain
0.53
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.65
Cadd
Benign
0.13
Dann
Benign
0.41
DEOGEN2
Benign
0.0018
T;T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.000010
N
M_CAP
Benign
0.0068
T
MetaRNN
Benign
0.088
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.41
N;N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
0.88
N;.
REVEL
Benign
0.032
Sift
Benign
0.12
T;.
Sift4G
Benign
0.12
T;T
Polyphen
0.0010
B;B
Vest4
0.14
MutPred
0.64
Gain of disorder (P = 0.0326);Gain of disorder (P = 0.0326);
MVP
0.030
MPC
0.018
ClinPred
0.025
T
GERP RS
-2.3
Varity_R
0.068
gMVP
0.016

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: rs761389569; hg19: chr1-227842530; API