8-80664915-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001033723.3(ZNF704):ā€‹c.827C>Gā€‹(p.Thr276Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000911 in 1,614,072 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000039 ( 0 hom., cov: 32)
Exomes š‘“: 0.000096 ( 2 hom. )

Consequence

ZNF704
NM_001033723.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.71
Variant links:
Genes affected
ZNF704 (HGNC:32291): (zinc finger protein 704) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.04983008).
BS2
High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF704NM_001033723.3 linkuse as main transcriptc.827C>G p.Thr276Arg missense_variant 6/9 ENST00000327835.7 NP_001028895.1
ZNF704NM_001367783.1 linkuse as main transcriptc.1349C>G p.Thr450Arg missense_variant 6/9 NP_001354712.1
ZNF704XM_017013725.2 linkuse as main transcriptc.851C>G p.Thr284Arg missense_variant 6/9 XP_016869214.1
ZNF704XR_928797.3 linkuse as main transcriptn.1773C>G non_coding_transcript_exon_variant 6/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF704ENST00000327835.7 linkuse as main transcriptc.827C>G p.Thr276Arg missense_variant 6/91 NM_001033723.3 ENSP00000331462 P1
ZNF704ENST00000519936.2 linkuse as main transcriptc.1349C>G p.Thr450Arg missense_variant 6/95 ENSP00000427715
ZNF704ENST00000522040.5 linkuse as main transcriptn.374C>G non_coding_transcript_exon_variant 3/33

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152178
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
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:
0.00316
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000119
AC:
30
AN:
251488
Hom.:
1
AF XY:
0.000155
AC XY:
21
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.000202
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000359
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000703
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.0000965
AC:
141
AN:
1461894
Hom.:
2
Cov.:
32
AF XY:
0.0000990
AC XY:
72
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000452
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000603
Gnomad4 OTH exome
AF:
0.000232
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152178
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.0000724
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000109
Hom.:
0
Bravo
AF:
0.0000680
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000581
AC:
5
ExAC
AF:
0.0000988
AC:
12
EpiCase
AF:
0.000218
EpiControl
AF:
0.00

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 GeneticsJul 27, 2023The c.827C>G (p.T276R) alteration is located in exon 6 (coding exon 5) of the ZNF704 gene. This alteration results from a C to G substitution at nucleotide position 827, causing the threonine (T) at amino acid position 276 to be replaced by an arginine (R). 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
Benign
0.10
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
18
DANN
Benign
0.97
DEOGEN2
Benign
0.062
T
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.13
FATHMM_MKL
Benign
0.60
D
LIST_S2
Benign
0.65
T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.050
T
MetaSVM
Benign
-0.58
T
MutationAssessor
Benign
0.35
N
MutationTaster
Benign
0.80
D
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.25
Sift
Benign
0.50
T
Sift4G
Benign
0.61
T
Polyphen
0.0020
B
Vest4
0.29
MVP
0.068
MPC
0.69
ClinPred
0.026
T
GERP RS
6.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.13
gMVP
0.26

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs140769308; hg19: chr8-81577150; API