1-40547047-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152373.4(ZNF684):​c.724C>A​(p.Pro242Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,614,072 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

ZNF684
NM_152373.4 missense

Scores

3
7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.75
Variant links:
Genes affected
ZNF684 (HGNC:28418): (zinc finger protein 684) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to act upstream of or within innate immune response and negative regulation of single stranded viral RNA replication via double stranded DNA intermediate. 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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF684NM_152373.4 linkc.724C>A p.Pro242Thr missense_variant Exon 5 of 5 ENST00000372699.8 NP_689586.3 Q5T5D7B3KSP5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF684ENST00000372699.8 linkc.724C>A p.Pro242Thr missense_variant Exon 5 of 5 1 NM_152373.4 ENSP00000361784.3 Q5T5D7
ZNF684ENST00000648542.1 linkc.724C>A p.Pro242Thr missense_variant Exon 6 of 6 ENSP00000497154.1 Q5T5D7
ZNF684ENST00000493756.1 linkn.591C>A non_coding_transcript_exon_variant Exon 3 of 3 3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152186
Hom.:
0
Cov.:
32
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
GnomAD4 exome
AF:
0.0000212
AC:
31
AN:
1461886
Hom.:
0
Cov.:
31
AF XY:
0.0000234
AC XY:
17
AN XY:
727242
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:
0.0000279
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152186
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74358
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:
0.00000756
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 20, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.724C>A (p.P242T) alteration is located in exon 5 (coding exon 4) of the ZNF684 gene. This alteration results from a C to A substitution at nucleotide position 724, causing the proline (P) at amino acid position 242 to be replaced by a threonine (T). 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
0.92
BayesDel_addAF
Benign
-0.097
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.21
T;T
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.32
.;T
M_CAP
Benign
0.0060
T
MetaRNN
Uncertain
0.69
D;D
MetaSVM
Benign
-0.79
T
MutationAssessor
Benign
1.7
L;L
PrimateAI
Uncertain
0.59
T
PROVEAN
Pathogenic
-7.7
D;.
REVEL
Benign
0.24
Sift
Pathogenic
0.0
D;.
Sift4G
Uncertain
0.0040
D;.
Polyphen
1.0
D;D
Vest4
0.52
MutPred
0.67
Loss of catalytic residue at P242 (P = 0.053);Loss of catalytic residue at P242 (P = 0.053);
MVP
0.10
MPC
0.39
ClinPred
1.0
D
GERP RS
3.3
Varity_R
0.68
gMVP
0.053

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: rs1477060840; hg19: chr1-41012719; API