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GeneBe

1-227655293-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001367909.1(ZNF678):c.1043C>A(p.Pro348His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,194 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: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZNF678
NM_001367909.1 missense

Scores

3
3
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.36
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26417997).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF678NM_001367909.1 linkuse as main transcriptc.1043C>A p.Pro348His missense_variant 4/4 ENST00000343776.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF678ENST00000343776.10 linkuse as main transcriptc.1043C>A p.Pro348His missense_variant 4/41 NM_001367909.1 P1
ZNF678ENST00000397097.4 linkuse as main transcriptc.1043C>A p.Pro348His missense_variant 2/21 P1
ZNF678ENST00000608949.5 linkuse as main transcriptc.226+817C>A intron_variant 1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000403
AC:
1
AN:
248100
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134678
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000546
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:
6.85e-7
AC:
1
AN:
1459194
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
725812
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:
0.00
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 GeneticsFeb 16, 2023The c.1208C>A (p.P403H) alteration is located in exon 4 (coding exon 4) of the ZNF678 gene. This alteration results from a C to A substitution at nucleotide position 1208, causing the proline (P) at amino acid position 403 to be replaced by a histidine (H). 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
0.66
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.41
Cadd
Benign
20
Dann
Uncertain
0.99
DEOGEN2
Benign
0.18
T;T
Eigen
Benign
0.031
Eigen_PC
Benign
-0.29
FATHMM_MKL
Benign
0.00043
N
M_CAP
Benign
0.0027
T
MetaRNN
Benign
0.26
T;T
MetaSVM
Benign
-0.81
T
MutationAssessor
Pathogenic
2.9
M;M
MutationTaster
Benign
0.61
N;N
PrimateAI
Benign
0.32
T
PROVEAN
Pathogenic
-7.1
D;.
REVEL
Benign
0.081
Sift
Uncertain
0.0030
D;.
Sift4G
Uncertain
0.0030
D;D
Polyphen
1.0
D;D
Vest4
0.24
MutPred
0.30
Loss of catalytic residue at P348 (P = 0.0702);Loss of catalytic residue at P348 (P = 0.0702);
MVP
0.15
MPC
0.10
ClinPred
0.96
D
GERP RS
1.6
Varity_R
0.45
gMVP
0.010

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: rs745468675; hg19: chr1-227842994; API